Studies of platelet and fibrinogen kinetics in 27 patients with hyperlipoproteinemia and 28 control subjects demonstrated shortened platelet survival and increased platelet turnover in seven patients with type III and 10 patients with type IV-V hyperlipoproteinemia (p < 0.01). There was no correlation between platelet survival time and specific lipid levels, vascular disease, sex or age. Platelet kinetics were not significantly altered from control values in eight patients with familial hypercholesterolemia. Platelet aggregation studies and fibrinogen kinetic measurements did not differ in any of the hyperlipoproteinemic groups of patients from those in control subjects. Despite significant changes in plasma lipids induced by clofibrate, platelet survival was significantly extended only in patients with type IV–V hyperlipoproteinemia (p < 0.05). These results are consistent with the hypothesis that atherogenesis in patients with types III–V hyperlipoproteinemia may be associated with a process of endothelial desquamation, and type Ila hyperlipoproteinemia may involve nondesquamating endothelial injury.