We assessed the impact of systematic risk factors on the vasomotor effects of inhibition of nitric oxide synthesis. N<sup>G</sup>-monomethyl- L-arginine (LNMMA) was infused intracoronarily at 4, 8 and 16 μmol/min followed by intracoronary bolus administration of 250 μg nitroglycerin. Computerized angiography was used to assess the changes in the diameter of coronary segments. During the LNMMA infusions there was no significant difference in LNMMA response between smokers and non-smokers (–5.5 ± 0.8 and –6.6 ± 0.6%, respectively) or between hypertensives and normotensives (–6.4 ± 1.1 and –6.1 ± 0.6%, respectively), but the response was less in hypercholesterolaemic patients (–4.5 ± 0.7 vs. –8.0 ± 0.6%, p < 0.05). Thus, the reduced nitric oxide activity is related to hypercholesterolaemia but not to smoking and hypertension.