The effects of long-term cigarette smoking on regional cerebral blood flow (rCBF) were studied in 67 normal male volunteers. All subjects were healthy volunteers without any past history of cerebral and pulmonary disease. rCBF decreased significantly with advancing age. Although there was no significant difference in rCBF between young smokers and nonsmokers, elderly smokers showed significantly lower rCBF than elderly nonsmokers. There was no difference in vital capacity and FEV 1.0% between smokers and nonsmokers in both young and elderly groups. The smokers, however, showed significantly lower V50 than the nonsmokers. PeCO2 in smokers was significantly lower than in nonsmokers. No significant differences were seen in hematocrit, antithrombin III, aggregating platelet, serum lipids and blood pressure between smokers and nonsmokers in both age groups. There was a significantly positive correlation between rCBF and PeCO2 in all groups. These results suggest that long-term smoking may reduce rCBF by means of hypocapnia, resulting from latent small airway disturbances, not by advancing cerebral arteriosclerosis.