Correlations between cigarette smoking and cerebral blood flow (CBF) were determined. The purpose of the present study was to determine whether the level of cigarette use is a significant predictor of regional CBF (rCBF) when age, gender, mean arterial blood pressure, total cholesterol, fasting blood glucose, hematocrit, and presence of ST-T change and left ventricular hypertrophy on electrocardiogram (ECG) are controlled. We studied a continuous sample of 40 asymptomatic individuals including 20 smokers and 20 nonsmokers. Subjects (mean age 66.2 yr) had an average smoking index of 456 +/- 485.1 (mean +/- standard deviation) [(Number of cigarette/d) x (years of smoking history)]. Regional CBF was measured using the intravenous 133Xe injection method. Simple linear regression and multivariate regression analyses were performed, which modeled regional cerebral blood flow as a function of smoking index and other cerebrovascular disease risk factors. The male-to-female ratio was higher in the group of smokers (18/2) than in the group of nonsmokers (2/18) (P < 0.01). The mean hematocrit of smokers was significantly higher than that of nonsmokers (P < 0.01). There were no significant differences in other variables tested between the two groups. Simple linear regression analysis demonstrated a significant negative correlation of smoking index with CBF in whole brain (r = -0.33; P < 0.05), the right hemisphere (r = -0.34; P < 0.05), right parietal cortex (r = -0.36; P < 0.05), right occipital cortex (r = -0.34; P < 0.05) and left parietal cortex (r = -0.33; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)