Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide which was originally isolated from ovine hypothalamus. PACAP exists in at least two biologically active forms, PACAP-38 and PACAP-27. The aim of this study was to establish the distribution, localization and smooth muscle effects of PACAP-38 and PACAP-27 in the human uteroplacental unit. For this purpose we used radioimmunoassay, immunocytochemistry and in vitro studies of the effect of the peptides on smooth muscle activity. Results: By radioimmunoassay both peptides were detected throughout the uteroplacental unit. The concentrations of PACAP-27 were in general low, ranging from 1-1 of the corresponding PACAP-38 concentrations. PACAP-immunoreactivity was localized in nerve fibres of the lower segment of the pregnant uterus, but the number of PACAP-immunoreactive nerves was very clearly reduced compared to the corresponding isthmic region of non-pregnant myometrial tissue. PACAP-immunoreactive fibres were not observed in placenta or in the umbilical cord. Both PACAP-38 and PACAP-27 caused a concentration-dependent relaxation on stem villous arteries and on the intramyometrial arteries. Neither of the peptides displayed any effect on non-vascular smooth muscle specimens from the term pregnant myometrium. In conclusion the findings suggest a vasoregulator role of PACAP in the human uteroplacental unit.