Increased visceral fat accumulation is a strong predictor of arterial hypertension. In this study, we explored the hypothesis that increased hepatic portal venous free fatty acid delivery results in increased blood pressure. Such an effect might explain the link between visceral obesity and hypertension. In nine conscious, instrumented rats, we studied the effects of 1-hour infusions of sodium oleate solution into the portal and femoral veins and infusions of sodium caprylate solution into the portal vein on 3 separate days. Basal blood pressure was not significantly different on the 3 study days. Mean arterial pressure increased 29±4 mm Hg during portal oleate infusion and 13±2 mm Hg during femoral oleate infusion (both significant increases over basal, P<.001). Mean arterial pressure did not change during portal caprylate infusion. The increase during portal oleate infusion was greater than that during femoral oleate infusion (P=.028). Heart rate rose during all three infusions; the increase was greatest during portal oleate infusion (334±4 to 412±2 beats per minute). During portal venous oleate infusion in five rats, plasma norepinephrine rose from 2.17±0.34 to 3.58±0.50 nmol/L, epinephrine rose from 0.79±0.28 to 1.84±0.44 nmol/L, and corticosterone rose from 147±55 to 1130±289 nmol/L. Three rats given portal venous oleate infusions for 1 week had increased blood pressure compared with baseline (mean increase, 16±4 mm Hg). These studies indicate that increases in portal venous fatty acid concentrations have significant pressor effects, perhaps mediated by increased sympathetic tone. Chronic increases in portal venous fatty acid levels may be responsible for the hypertension that accompanies visceral obesity.