We investigated the effect of intimal thickness in human coronary artery on the endothelium-dependent relaxation. Histamine (in the presence of cimetidine), substance P and A23187 potently relaxed arterial rings with intima thinner than 200 .mu.m. However, those relaxations diminished progressively in the artery with intimal thickness of 200-400 .mu.m, and disappeared at the thickness greater than 400 .mu.m. These results suggest that diffuse intimal thickening greater than 200 .mu.m may inhibit the diffusion of endothelium-derived relaxing factor.