BACKGROUND AND AIM: Intraluminal nutrients stimulate superior mesenteric artery (SMA) blood flow. Of the macronutrients, especially fat affects the magnitude of the SMA blood flow response to a meal. Little is known however on the influence of fat hydrolysis on SMA flow. METHODS: We compared in eight healthy volunteers the SMA flow response (Doppler ultrasonography) to continuous intraduodenal fat perfusion (LCT, 240 kCal h(-1)) during conditions with normal hydrolysis (placebo, control), increased hydrolysis (pancreatic enzyme supplementation; 50 kU lipase) and impaired hydrolysis (orlistat 240 mg). RESULTS: Intraduodenal LCT significantly (P<0.01) increased SMA flow in all experiments over basal. The SMA flow response to fat during pancreatic enzyme supplementation (1.49 +/- 0.1 l min(-1)) was significantly (P<0.05) higher compared with placebo (1.11 +/- 0.16 l min(-1)). Lipase inhibition with orlistat did not significantly affect fat stimulated SMA flow compared with placebo: 0.89 +/- 0.08 l min(-1) versus 1.11 +/- 0.16 l min(-1). CONCLUSIONS: Administration of pancreatic enzymes significantly increases fat stimulated SMA flow. Fat digest products in the intestinal lumen contribute to the regulation of SMA blood flow.