Anti-coagulation in experimental GN [glomerulonephritis] has not uniformly reduced inflammation and prevented functional impairment. Platelet thrombi are occasionally present in nephritic kidneys. Platelet aggregation may play a fundamental role and inhibition of aggregation may be of therapeutic value. The effect of selective platelet depletion on acute IC [immune complex] GN in the rabbit was evaluated. IC GN was induced with bovine albumin, and platelet depletion with [goat] APS [anti-platelet antiserum]. Platelet depletion preceded proteinuria by more than 36 h and was sustained for 5 days. Platelet accumulation within the nephritic kidney was quantitated with Cr-labeled platelets. The hemodynamic effect of parenteral administration of APS on the evolution of IC GN was assessed by comparing i.v. with i.p. administration. Thrombocytopenia in the absence of hypotension had no inhibitory effect on IC GN, nor was there platelet accumulation within the nephritic kidneys of the platelet-depleted animals. Platelet aggregation is not essential in the pathogenesis of IC GN and inhibition of platelet aggregation may be of little value.