Prepro-TRH 178-199, a peptide with corticotropin release inhibiting activity at the pituitary, on the Porsolt forced swim test (FST) of depressive behavior in rats. Prepro TRH (178-199) derived from prepro-TRH inhibits basal and CRF-stimulated ACTH synthesis and secretion. Biological activity of this peptide resides in the C-terminal fragment as prepro-TRH 178-199 and prepro-TRH 191-199 were equally potent in the FST. These data suggest that endogenous prepro-TRH 178-199 with its antidepressant-like activity might contribute to the etiology or manifestation of depressive behavior.