OBJECTIVE: The present study was undertaken to investigate whether chronic smoking alters the vasodilatory capacity in the microcirculation. METHODS: We assessed, in habitual cigarette smokers, the forearm skin blood flow response to iontophoretically applied acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside. Postocclusive forearm reactive hyperemia was also explored. The skin blood flow responses were determined with a laser-Doppler flowmeter that allowed us to scan the surface after acetylcholine and sodium nitroprusside application. RESULTS: Forty healthy male volunteers were included. Twenty subjects were aged 20 to 35 years and 20 subjects were aged 40 to 60 years. We studied the following 4 groups of 10 subjects each: group 1, younger smokers (mean of 7.2 pack-years); group 2, older smokers (mean of 30 pack-years); group 3, younger nonsmokers; and group 4, older nonsmokers. On the day of the experiment, the subjects of groups 1 and 2 were asked to smoke at least 15 cigarettes from the morning until the afternoon, when the experiments were performed. No significant difference in the studied parameters was observed between younger smokers and younger nonsmokers. In older smokers, however, both acetylcholine- and sodium nitroprusside-induced skin blood flow increases were significantly attenuated in comparison with nonsmokers. Heart rate also was significantly blunted by long-term cigarette smoking in older subjects. CONCLUSION: These data show that the vasodilatory response of the skin microvasculature is impaired in subjects who have smoked cigarettes for many years. This abnormality involves both endothelium-dependent and endothelium-independent responses.