The effects of an intracoronary infusion of N(G)-monomethyl-L-arginine (LNMMA) followed by intracoronary administration of nitroglycerin in non-stenotic proximal and distal coronary segments were studied in 11 patients with coronary artery disease and in 19 subjects with "normal arteriograms". In normal subjects, LNMMA induced significant constriction (p<0.01) of proximal and distal vessels in non-smokers and smokers. In normal non-smokers, the reduction in coronary luminal diameter of proximal segments was significantly greater compared to normal smokers (p<0.05). In patients with coronary artery disease, LNMMA induced significant constriction of proximal and distal vessels in smokers, and only distal constriction in non-smokers (p<0.01). The reduction in coronary luminal diameter of the distal segments in normal smokers, and in both groups in patients with coronary artery disease was significantly greater compared with proximal segments (p<0.05). Therefore, the difference in vasomotor response to LNMMA in relation to smoking is localised to the proximal coronary segments.