Hi,

Every update/installation of packages by BiocManager fails with a following typical error message;

*   Trying 99.84.168.92...
* TCP_NODELAY set
* Connected to bioconductor.org (99.84.168.92) port 443 (#0)
* ALPN, offering http/1.1
* Cipher selection: ALL:!EXPORT:!EXPORT40:!EXPORT56:!aNULL:!LOW:!RC4:@STRENGTH
* successfully set certificate verify locations:
*   CAfile: /etc/ssl/cert.pem
  CApath: none
* SSL connection using TLSv1.2 / ECDHE-RSA-AES128-GCM-SHA256
* ALPN, server accepted to use http/1.1
* Server certificate:
*  subject: OU=Domain Control Validated; CN=*.bioconductor.org
*  start date: Oct  5 14:24:38 2016 GMT
*  expire date: Oct  3 18:30:38 2019 GMT
*  subjectAltName: host "bioconductor.org" matched cert's "bioconductor.org"
*  issuer: C=US; ST=Arizona; L=Scottsdale; O=GoDaddy.com, Inc.; OU=http://certs.godaddy.com/repository/; CN=Go Daddy Secure Certificate Authority - G2
*  SSL certificate verify ok.
> GET /biocLite.R HTTP/1.1
Host: bioconductor.org
User-Agent: libcurl/7.54.0
Accept: */*

< HTTP/1.1 200 OK
< Content-Length: 8355
< Connection: keep-alive
< Server: Apache/2.4.18 (Ubuntu)
< Last-Modified: Wed, 05 Jun 2019 12:00:02 GMT
< Accept-Ranges: bytes
< Date: Sun, 25 Aug 2019 14:05:11 GMT
< ETag: "20a3-58a925659f7b8"
< Cache-Control: max-age=60
< Age: 29
< X-Cache: Hit from cloudfront
< Via: 1.1 e385fbaea7c648ad7e4ea77cdc0acd94.cloudfront.net (CloudFront)
< X-Amz-Cf-Pop: ORD52-C2
< X-Amz-Cf-Id: w2fd4plWyxXXjT9rHPnZnvHb0dc7oOh4q-HRYvg3xKyzE1vWqWwSnQ==
< 
* Connection #0 to host bioconductor.org left intact
Error: With R version 3.5 or greater, install Bioconductor packages using BiocManager; see https://bioconductor.org/install
Execution halted

If I use R --vanilla I don't run into this issue but otherwise (even in the absence of custom Makevars and .Rprofile), this happens constantly.

My system;

sw_vers
ProductName:    Mac OS X
ProductVersion: 10.14.6
BuildVersion:   18G87

R version (brew installed)

R: stable 3.6.1 (bottled)
Software environment for statistical computing
https://www.r-project.org/
/usr/local/Cellar/R/3.6.1_1 (2,121 files, 56.8MB)
  Poured from bottle on 2019-08-24 at 08:33:00
From: https://github.com/Homebrew/homebrew-core/blob/master/Formula/r.rb
==> Dependencies
Build: pkg-config ✔
Required: gcc ✔, gettext ✔, jpeg ✔, libpng ✔, openblas ✔, pcre ✔, readline ✔, xz ✔

Sessioninfo:

> sessionInfo()
R version 3.6.1 (2019-07-05)
Platform: x86_64-apple-darwin18.6.0 (64-bit)
Running under: macOS Mojave 10.14.6

Matrix products: default
BLAS:   /System/Library/Frameworks/Accelerate.framework/Versions/A/Frameworks/vecLib.framework/Versions/A/libBLAS.dylib
LAPACK: /usr/local/Cellar/openblas/0.3.7/lib/libopenblasp-r0.3.7.dylib

Random number generation:
 RNG:     Mersenne-Twister 
 Normal:  Inversion 
 Sample:  Rounding 

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] BiocManager_1.30.4    edgeR_3.26.7          limma_3.40.6          Vennerable_3.1.0.9000

loaded via a namespace (and not attached):
 [1] enrichplot_1.4.0       bit64_0.9-7            RColorBrewer_1.1-2     progress_1.2.2        
 [5] httr_1.4.1             UpSetR_1.4.0           tools_3.6.1            backports_1.1.4       
 [9] R6_2.4.0               plotROC_2.2.1          DBI_1.0.0              lazyeval_0.2.2        
[13] BiocGenerics_0.30.0    colorspace_1.4-1       tidyselect_0.2.5       gridExtra_2.3         
[17] prettyunits_1.0.2      bit_1.1-14             compiler_3.6.1         graph_1.62.0          
[21] Biobase_2.44.0         xml2_1.2.1             triebeard_0.3.0        scales_1.0.0          
[25] ggridges_0.5.1         RBGL_1.60.0            stringr_1.4.0          digest_0.6.20         
[29] DOSE_3.10.2            pkgconfig_2.0.2        rlang_0.4.0            rstudioapi_0.10       
[33] RSQLite_2.1.2          gridGraphics_0.4-1     farver_1.1.0           jsonlite_1.6          
[37] BiocParallel_1.18.1    GOSemSim_2.10.0        dplyr_0.8.3            magrittr_1.5          
[41] ggplotify_0.0.4        GO.db_3.8.2            Matrix_1.2-17          Rcpp_1.0.2            
[45] munsell_0.5.0          S4Vectors_0.22.0       viridis_0.5.1          yaml_2.2.0            
[49] stringi_1.4.3          ggraph_1.0.2           MASS_7.3-51.4          plyr_1.8.4            
[53] qvalue_2.16.0          grid_3.6.1             blob_1.2.0             parallel_3.6.1        
[57] ggrepel_0.8.1          DO.db_2.9              crayon_1.3.4           lattice_0.20-38       
[61] cowplot_1.0.0          splines_3.6.1          hms_0.5.1              locfit_1.5-9.1        
[65] zeallot_0.1.0          pillar_1.4.2           fgsea_1.10.1           igraph_1.2.4.1        
[69] ggpubr_0.2.2           ggsignif_0.6.0         reshape2_1.4.3         stats4_3.6.1          
[73] fastmatch_1.1-0        glue_1.3.1             data.table_1.12.2      vctrs_0.2.0           
[77] tweenr_1.0.1           urltools_1.7.3         gtable_0.3.0           purrr_0.3.2           
[81] polyclip_1.10-0        tidyr_0.8.3            assertthat_0.2.1       ggplot2_3.2.1         
[85] ggforce_0.3.1          europepmc_0.3          viridisLite_0.3.0      tibble_2.1.3          
[89] clusterProfiler_3.12.0 rvcheck_0.1.3          AnnotationDbi_1.46.1   memoise_1.1.0         
[93] IRanges_2.18.2

Any pointers to fix this issue will be appreciated.

I read your post to say that you have no problems with R --vanilla, but do if starting with plain R.

The ?Startup help page describes which files are referenced when R starts up, and also which files --vanilla causes R to skip. Review the files (e.g., start R --vanilla and source() each file that exists) to identify the (non-default) content that triggers the verbose output during download.

I found a culprit. I have three R project directories and home directory and each of those have .Rprofile. I thought I commented out/deleted "source("https://bioconductor.org/biocLite.R") from all the .Rprofile but I missed removing it from one of them. Now the problem solved. Thanks @shahryary and Martin Morgan for suggestions.