Repressor element I (RE-1) is a negative, cis-acting regulatory element that interacts with the transcription factor RE-1-silencing transcription factor (REST). REST represses gene expression by two repressor domains that recruit other factors including mSin3 and CoREST. RE-1 has been identified inan increasing number of neuronal-specific genes, and recently, functional REST sites have also been discovered in VIP and PACAP genes. In the present article, we demonstrated for the first time that RE-1sites are present in the 5' flanking regions of several secretin/PACAP/VIP genes by in silico analysis. This observation suggests that RE-1/REST is a common negative regulatory pathway of this peptide family.