Abstract.Localization and functional effects of vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), two peptides derived from a common precursor molecule, were investigated in isolated preparations from human penile corpus cavernosum (CC) and circumflex vein (CV). VIP‐ and PHM‐immunoreactivity (IR) was demonstrated in both CC and CV. The concentrations of VIP‐IR and PHM‐IR in CC tissue were 54.4PM15.3, and 42.0 PM7.5 pmol g‐1wet weight respectively with a VIP/PHM ratio of 1.5PM0.4 (meanPMSEM). The corresponding values for CV tissues were 28.0 PM7.7 and 9.6 PM2.6 pmol g‐1wet weight with a VIP/PHM ratio of 3.1PM0.4. CC and CV displayed VIP‐ and PHM‐IR confined to nerve fibres in close relation to bundles of smooth muscle cells and blood vessels in both tissues.In vitro, VIP and PHM had no effects in unstimulated tissue preparations. Both peptides concentration‐dependently (10‐9‐10‐6m) relaxed CC and CV preparations precontracted with 3 times 10‐6m noradrenaline. In CC the maximum relaxant effect of VIP and PHM was 22PM 11 % and 9 PM 9% and in CV the corresponding values were 82 PM 8% and 93 PM3% respectively. The present study supports the hypothesis of VIP and PHM as neurotransmitters and/or neuromodulators in the nervous c