1. The present study was performed to examine and compare the effect of increasing doses of vasoactive intestinal polypeptide (VIP) on vaginal blood flow following vaginal subepithelial and intravenous injection in normal women. 2. Local vaginal blood flow was measured by a heated oxygen electrode. 3. Peripheral blood samples were collected throughout the experiments for VIP analysis by radioimmunoassay. 4. Both subepithelial and intravenous injections induced a significant and dose-dependent increase in vaginal blood flow (P less than 0.05), displaying the same efficacy, potency and sensitivity. 5. The vaginal flow values correlated with the corresponding plasma VIP concentrations after both routes of administration. 6. The systemic vascular side effects; that is, flushing, hypotension and tachycardia, were observed following both subepithelial and intravenous injection. 7. The findings indicate that the effect of VIP on vaginal blood flow irrespective of route of administration is part of a systemic vasodilatory effect rather than a local response.