The acute effects of smoking a single cigarette on peripheral blood flow were investigated by laser-Doppler flowmetry in nine patients with Raynaud's phenomenon and 12 normal controls. In regular smokers, a marked fall in finger blood flow was demonstrated, but this was not present in non- or irregular smokers. In addition, no effect on capillary blood flow was found. There was no difference between subjects with and without Raynaud's phenomenon. In five normal, non-smoking volunteers, 2.4 g of aspirin for 3 days resulted in a similar fall in blood flow due to a single cigarette. These results suggest that regular smoking sensitizes the peripheral vasculature to the vasoconstricting effects of the next cigarette, and that at least part of this sensitization is mediated by the inhibition of endothelial prostacyclin synthesis. Patients with Raynaud's phenomenon, either primary or secondary, are no more sensitive than normal subjects, but should nevertheless avoid cigarette smoking.