p300/CBP are versatile transcriptional coacti-vators that participate in many physiological processes, including cell cycle control, differentiation and apoptosis. p300/CBP possess histone acetyltransferase (HAT) activity and they are involved in transcriptional regulation by acetylating histone and nonhistone proteins. Moreover, they act as protein bridges connecting specific transcription factors to the basal transcription machinery and provide a scaffold to integrate multiple transcription cofactors. Several studies suggest that p300/CBP may serve as tumor suppressors since mutations or translocations in p300/Cbp genes have been observed in a number of cancers. Furthermore, in many neurodegenerative diseases, inhibition of p300/CBP function may be one of the underlying causes of cytotoxicity. Several studies have demonstrated that p300/CBP are implicated in the regulation of many interleukin genes. This review focuses on the structures and functions of p300/CBP and their roles in the regulation of interleukin genes based on the work performed in our laboratory.