Since rat platelets fully responsive to thrombin and collagen did not respond by releasing 3H-serotonin with up to 10 micrograms/ml of synthetic PAF-acether, the rat, contrariwise to the rabbit, was considered to be an appropriate model to study the actions of PAF-acether not mediated through the activation of platelets and the subsequent release of their inflammatory mediators. We developed an experimental approach using 57Co and 113Sn radiolabeled microspheres to assess the effect of PAF-acether on cardiac output, peripheral vascular resistance, and regional flows and resistance. The effect on vascular permeability and blood volume was studied by measuring the clearance of 125I-HSA and the variations of the hematocrit. A significant fall in blood pressure and peripheral vascular resistance was found with doses of PAF-acether ranging from 0.05 to 5 micrograms. Moreover, the higher doses of PAF-acether also induced a marked depletion of blood volume. A significant fall in spleen, coronary, and kidney output, but not in cardiac output, was also found. Our data show that PAF-acether, by itself, induces a drop in peripheral vascular resistance and, at higher doses, also in circulating volume, accounting for both by the hypotensive effect. The redistribution of cardiac output seems to be the expression of a nonuniform action of the compound on the vascular resistance of the different organs.