Samples of proximal saphenous vein were obtained from heavy smokers and non-smokers: 28 were obtained at varicose vein surgery and eight at infrainguinal bypass surgery. The veins were prepared for histological examination and for mounting in an organ bath to measure changes in isometric tension. Vein rings from both smokers and non-smokers responded equally to sodium nitroprusside, a reagent that acts directly on smooth muscle cells, undergoing 90–100 per cent relaxation. The mean(s.e.m.) maximum relaxation in response to bradykinin of rings obtained at varicose vein surgery was 50·0(5·3) per cent in non-smokers compared with only 31·6(2·2) per cent in smokers (P = 0·03). Similarly, in specimens obtained at bypass surgery the mean(s.e.m.) maximum relaxation in smokers was only 25·1(6·3) per cent compared with 48·4(4·1) per cent in smokers (P = 0·04). Relaxation in response to the bradykinin stimulus was abolished in the presence of L-nitroarginine methyl ester, a specific inhibitor of the synthesis of endothelium-derived relaxing factor (EDRF). Preincubation of the vein rings with L-arginine, the precursor of EDRF, did not increase the vasorelaxation in smokers. The mean(s.e.m.) maximum relaxation in response to the calcium ionophore A23187 was 53·5(3·8) per cent in non-smokers compared with only 27·0(4·9) per cent in smokers (P = 0·01). The results indicate that heavy smokers have impaired release of EDRF in response to both bradykinin and calcium ionophore. This impairment may increase vasomotor tone, platelet aggregation and smooth muscle proliferation, thereby resulting in an increased risk of graft occlusion.