The effect of lipid peroxide (15-hydroperoxy arachidonic acid) on the activity of lipoprotein lipase was investigated. The activities were examined in 2 enzyme species : the lipoprotein lipase bound to the coronary vessels of the rat heart and that solubilized in the human post-heparin plasma. As a substrate, ³H-labelled human chylomicron was used. Lipid peroxide decreased the maximal velocity of the reaction between the chylomicron and lipoprotein lipase on the vascular surface. In the post-heparin plasma, the lipid peroxide decreased the maximal hydrolysis rate, but did not change the half life time in the unsaturated reaction. It is suggested that lipid peroxide directly damages a part of the membrane-bound lipoprotein lipase, and that the degeneration of cell membranes and the vasoconstriction caused by lipid peroxide will additionally disturb the hydrolysis of the plasma triglyceride on the vascular surface.