Dear Jim, I have a similar question, but it's for limma. I noticed when I want to make contrasts among the three levels (A, B, and C) of a factor, limma does not make adjustment for the multiple contrasts and only make adjustment within each contrast by whatever method I specify in the decideTests function. Should I adjust for the multiple contrast? Does your argument about the dependency among the GO terms apply to this question? The following are the R code for the contrasts. Thanks. contrast.matrix <- makeContrasts(A-C,B-C,0.5*(A+B)-C, levels=design) fit2 <- contrasts.fit(fit, contrast.matrix) fit2 <- eBayes(fit2) results <- decideTests(fit2,p.value=0.05,adjust.method="fdr") Chunyan Biostatistician I Center for Epidemiology and Biostatistics Cincinnati Children's Hospital Medical Center 513-636-9763