We investigated the early postnatal changes of the mesenteric circulation and its relation to the systemic circulation in 15 preterm infants. The infants were studied before the first feeding on d 1 and pre- and postprandially on d 3, 4, 5, and 7. Blood flow velocity was measured by ultrasound Doppler in the superior mesenteric artery, middle cerebral artery, and the aortic orifice for cardiac output calculations. Blood pressure and heart rate were monitored. From d 1 to d 3, the preprandial stroke volume decreased [1.5 +/- 0.3 to 1.3 +/- 0.2 mL/kg (mean +/- SD), p < 0.05], whereas blood pressure (36 +/- 3 to 50 +/- 7 mm Hg, p < 0.001), superior mesenteric artery mean velocity (Vmean) (0.17 +/- 0.08 to 0.30 +/- 0.11 m/s, p < 0.05), and middle cerebral artery Vmean increased (0.15 +/- 0.05 to 0.22 +/- 0.03 m/s, p < 0.001). From d 3 through d 7, the preterm infants demonstrated higher preprandial end diastolic flow velocity in the superior mesenteric artery than we previously reported in term infants (0.15 +/- 0.05 versus 0.12 +/- 0.04, p < 0.05). Like the term infants, preterm infants increased their superior mesenteric artery Vmean by 83% postprandially and maintained a stable cerebral circulation with feeding. Unlike the term infants, feeding in the preterm infants induced a blood pressure decrease (51 +/- 6 to 48 +/- 6 mm Hg, p < 0.01) and a cardiac output increase (176 +/- 30 to 188 +/- 32 mL/kg/min, p < 0.001). These findings suggest that, in contrast to term infants, healthy preterm infants require compensatory systemic hemodynamic changes in response to feeding.