Acute selective intrahepatic hypertension (IHH) is associated with the renal tubular retention of sodium in volume expanded dogs. To determine if acute selective IHH per se, without volume loading or ascites sequestration, would blunt the natriuretic response to i.v. infusions of atrial natriuretic peptide (ANP), 175 ng/kg/min of the 1-28 rat peptide was infused into 6 hydropaenic dogs where intrahepatic hydrostatic pressures were normal, and again, following the portal infusion of histamine, a maneuver known to selectively increase postsinusoidal resistance, within the hepatic microcirculation and so raise intrahepatic sinusoidal pressure. In 6 healthy dogs, while histamine 4.0 micrograms/min free base on average was being infused into a femoral vein, the infusion of ANP increased sodium excretion by 168 microEq/min, compared to 160 microEq/min when the same dose of histamine was being infused into the portal vein (portal pressure increased by 46% or 6 cm H2O). These changes in sodium excretion were not significantly different. Urine flow rate increased by 1.5 ml/min in the control phase and by 1.4 ml/min during intrahepatic hypertension (NS). Although the ANP infusion did not alter GFR or CPAH during the control phase, during IHH, ANP caused GFR to rise significantly by 20%, while there was no change to CPAH. Despite the increment in GFR, the natriuretic response during IHH was not different from that observed during the control phase of the study. We conclude that acute IHH per se does not blunt the renal tubular natriuretic response to ANP.