1. Intestinal absorption and blood flow in anaesthetized dogs was determined after I.V. infusion of vasoactive intestinal polypeptide (VIP) (1.75-175 ng/min) to determine the contribution of the cardiovascular changes to transport. 2. 22Na and 3H2O were utilized to determine the unidirectional fluxes of Na and H2O from saline perfused through the ileal lumen and the clearances of 3H2O were used to determine total and absorptive site blood flow. 3. Net Na and H2O absorption were reversed to secretion by VIP at 175 ng/min due to a significant decrease in unidirectional absorptive fluxes and smaller increases in secretory fluxes. 4. Arterial pressure and absorptive site blood flow were reduced in proportion to the changes in Na and H2O fluxes. 5. Total and absorptive site blood flow decreased and the blood flow resistances increased. 6. Prior treatment with guanethidine to suppress sympathetic effects did not greatly affect the responses to VIP. Prior treatment with atropine to suppress cholinergic effects inhibited most of the effects of VIP. 7. Absorptive site blood flow was linearly related to absorptive fluxes of Na and H2O but with different slopes for results from atropinized dogs as compared to those from dogs given VIP alone or VIP plus guanethidine. 8. It was concluded that VIP reduces gut absorption through a generalized cardiovascular effect and also through a mechanism which depends on the release of ACh by the gut.