We studied the direct effects of dopamine on hepatic blood flow using DHP under HVI. Dopamine was given to mongrel dogs through either the right antecubital vein (group I: n = 3), the hepatic artery-HA (group II: n = 7) or the portal vein-PV (group III: n = 6). In groups II and III, DHP under HVI was performed to eliminate the cardiovascular influence caused by the extraregional distribution of dopamine. In group I, HA/AO decreased from 2 +/- 10 to 29 +/- 9% with infusions of dopamine from 1 to 10 micrograms/kg/min. The peak increase in PV/AO was only 14 +/- 11%. In groups II and III, plasma concentrations of dopamine in the hepatic venous blood were reduced to as low as 2.7 +/- 1.6% after DHP, and AO flow remained unaltered. Dopamine infusions in doses from 0.25 to 10 micrograms/kg/min through HA and PV resulted in dose dependent reductions of HA/AO from 4 +/- 14 and 10 +/- 9% to 42 +/- 12 and 51 +/- 11%, respectively. In contrast, PV/AO remained unchanged. Although alpha 1 antagonist reversed these hemodynamic effects, no remarkable change was observed with DA1-antagonist. In conclusion, dopamine seems to act at the site of either sinusoidal or post-sinusoidal level probably as an alpha-agonist. In addition to dopamine's effect on PV flow, our study indicates that increased attention should be given to its activity in reducing HA flow.