Using an antiserum to a 22-amino acid synthetic peptide corresponding to sequence 178-199 of the precursor of thyrotropin-releasing hormone (pro-TRH), we have studied by immunocytochemistry the distribution of immunoreactive pro-TRH in the rat brain. Immunostaining found in several regions of the brain had a distribution similar to that previously reported for TRH. Reaction product was found in both neuronal cell bodies and processes. These results indicate that peptide(s) derived from pro-TRH are transported along the axons with TRH itself. Moreover, the presence of immunoreactive nerve endings in different areas including the median eminence suggests that this material might have a neuromodulator/neurotransmitter role in the central nervous system and could also be released into the pituitary portal plexus.