We have developed a model of endotoxemic acute renal failure in the anesthetized male rat in which acute endotoxin infusion induces renal vasoconstriction and decreased glomerular filtration rate (GFR) in the absence of systemic hypotension. Because increased levels of platelet activating factor (PAF) have been observed in experimental models of endotoxemia, we pretreated rats with PAF receptor antagonist BN 52021 or SRI 63-675 before administering endotoxin. Compared with treatment with vehicle, treatment with BN 52021 led to significant preservation of RBF, GFR, and urine flow rate. Pretreatment with SRI 63-675 resulted in significant improvement in RBF while completely preventing the fall in GFR and urine flow rate. Intrarenal artery infusion of exogenous PAF (30 ng/kg/min) resulted in renal vasoconstriction, decreased GFR, and oliguria. These effects were also prevented by pretreatment with SRI 63-675. Thus, the adverse renal hemodynamic effects of endotoxemia were blunted or prevented by pretreatment with PAF receptor antagonists. We conclude that endogenously produced PAF is an important mediator of endotoxemic acute renal failure.