Renal arterial fibromuscular dysplasia (FMD) is a significant cause of renovascular hypertension, especially in younger females. Tobacco constituents have been shown to stimulate proliferation and synthetic activity of cultured human vascular smooth muscle cells. We examined the relationship between smoking and severity of FMD in a group of 50 subjects with the multifocal form of renal arterial FMD. A detailed smoking history was obtained by interview, clinical data at diagnosis of FMD were obtained from medical records, and angiograms were reviewed. Clinical and angiographic features were compared between smokers and non-smokers. Twenty-four subjects were smokers. At the time of diagnosis of FMD, smokers were of younger mean age than non-smokers (38.7 years vs 48.9 years, P < 0.01), had a shorter median history of hypertension (1.5 years vs 8.5 years, P < 0.05), and had a higher prevalence of unilateral renal atrophy (67% vs 27%, P < 0.01). The distribution of age at diagnosis of FMD was unimodal in non-smokers and bimodal, with a discrete group of younger subjects, in smokers. We conclude that cigarette smoking is associated with an earlier onset and increased severity of disease in a susceptible subgroup of patients predisposed to multifocal renal arterial FMD.