Smoking has been known to cause endothelial dysfunction and is an important risk factor for ischemic stroke. In our study we investigated whether chronic cigarette smoking affects the cerebral blood flow velocity response to a physiological, visual stimulus. By using a visual cortex stimulation paradigm, the flow velocity response in the posterior cerebral arteries (PCA) was measured bilaterally, in 32 young healthy adults (16 smokers, 16 nonsmokers). The stimulation protocol consisted of 10 cycles with a resting phase of 20 s and a stimulating phase of 40 s for each cycle. Besides functional transcranial Doppler (TCD), laboratory tests and measurement of intima-media-thickness (IMT) were also performed. Repeated-measure analysis of variance (ANOVA) was used to detect differences in visually evoked relative flow velocity time courses between smokers and nonsmokers. Repeated-measure ANOVA revealed marked difference in the peak systolic flow velocity time courses between smokers and nonsmokers (p< .001). Maximum percent change of visually evoked flow velocity after visual stimulation was 19+/-4% and 30+/-3% in smokers and nonsmokers, respectively (p< .0001). IMT values did not indicate atherosclerosis in young smokers. Infectious disease and hyperlipidemia were also ruled out by measurement of sensitive C-reactive protein and serum lipids. This is the first functional TCD study demonstrating impaired visually evoked flow velocity response caused by chronic cigarette smoking in otherwise healthy, young subjects. The impaired cerebral vasodilatory mechanism together with atherosclerosis may influence stroke occurrence and outcome in chronic smokers.