The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects, were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. One hundred and eleven subjects, who had no abnormalities in neurological examinations nor in CT scans, were divided into two groups: smokers (37) and non-smokers (74). Those who had a smoking index (Number of cigarettes/day) × (years of smoking history) greater than 200 were designated as smokers. The mean smoking index of smokers was 760. Sixty-two of the 74 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 17. In the male, CBF was significantly lower in smokers than in non-smokers (mean CBF, 12.5% lower in smokers, p less than 0.001). Increased reduction of CBF with advancing age was also observed. Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduces CBF. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels.