Objective. Serotonin is a vasoactive neuroendocrine substance and serotonergic drugs are promising agents for the treatment of functional gastrointestinal disorders. The effect of serotonin on superior mesenteric blood flow in humans is unknown. The aim of this study was to examine the effect of exogenous serotonin on superior mesenteric artery blood flow, as estimated by the resistance index with Doppler ultrasound, in healthy human volunteers. Methods. Six fasting healthy adult volunteers of both gender were studied. Transabdominal Doppler ultrasound was used to evaluate the effects of either a standard meal or intravenous infusion of serotonin (2.5–20 nmol/kg/min) on superior mesenteric artery resistance index, platelet-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram. Results. All subjects had the same patterns of response to meal and serotonin stimulation. Meal stimulation decreased mean resistance index from 0.84±0.04 to 0.72±0.02 (p=0.0004) and increased platelet-depleted-plasma levels of serotonin from 50±36 to 61±46 nmol/l (p=0.04) – demonstrating an intact normal neuro-endocrine intestinal system. Serotonin stimulation increased mean resistance index from 0.82±0.04 to 0.88±0.03 (p=0.006) and mean platelet-depleted-plasma levels of serotonin from 44±24 to 83±37 nmol/l (p=0.03). Most subjects reported minor short-lived adverse effects. Electrocardiogram was unchanged during all examinations. Conclusions. We conclude that intravenous infusion of serotonin increases resistance index of the superior mesenteric artery in healthy adult volunteers.