The human vagina and uterus are heavily innervated by VIP-containing nerve fibres. In the present study, we have measured vaginal blood flow, transmucosal oxygen tension and uterine smooth muscle activity during stepwise intravenous infusion of vasoactive intestinal polypeptide (VIP) (0, 100, 300, 900 pmol kg-1 h-1) in non-pregnant women. Vaginal blood flow was measured by the heat clearance technique, transmucosal oxygen tension by an O2-electrode and uterine activity by a micro-tip pressure catheter in the uterine cavity. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral venous blood were monitored. VIP induced a concentration-dependent increase in vaginal blood flow. The transmucosal oxygen tension was not significantly changed by VIP. The maximum dose of VIP decreased systolic as well as diastolic blood pressure and increased pulse frequency. VIP inhibited uterine activity. These findings suggest that VIP participates as a neurotransmitter in the control of genital physiological responses.