The isolated canine spleen was perfused at constant flow with continuous recording of splenic arterial perfusion pressure (SAPP) and spleen weight. Intra-arterial injections of the thromboxane A2 (TXA2) mimetic U46619 caused dose-related increases in splenic arterial perfusion pressure (SAPP) of short duration (ED50 0.31 nmol). There were very small changes in spleen weight accompanying any of the vasoconstrictor responses to U46619. The stable analogue of prostacyclin, iloprost, caused dose-dependent reductions in SAPP (ED50 1.3 nmol) indicating vasodilation. There were no changes in spleen weight to any doses of iloprost indicating a lack of action on capsular smooth muscle. Similarly, the nitric oxide (NO) mimetic sodium nitroprusside caused dose-related reductions in SAPP of short duration (ED50 5.8 nmol). No changes in spleen weight accompanied splenic vasodilator responses to any dose of sodium nitroprusside (SNP). The results indicate the potential actions and intrinsic potency of three endogenous vasoactive substances and provide information about their relative roles in the control of the splenic microcirculation in situations when they are released.