Corticotropin-releasing hormone (CRH) is a 41-amino acid neuropeptide which increases the transcription of the proopiomelanocortin (POMC) gene, as well as the biosynthesis and secretion of POMC-derived peptides. Using a specific human CRH radioimmunoassay we have shown that human T-lymphocytes contain immunoreactive CRH. We studied the effects of phytohemagglutinin (PHA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on the biosynthesis of CRH in human T-lymphocyte cell cultures. A significant increase in CRH mRNA levels was observed in human lymphocytes after 12 h of PHA/TPA treatment, while the levels decreased after 22 h. These findings could imply an immunomodulatory role for CRH that could be due to autocrine and/or paracrine interactions.