In order to evaluate a possible relation between cigarette smoking and prevalence of diabetic microangiopathy, a series of 180 consecutive patients suffering from insulin-dependent juvenile-onset diabetes mellitus with different durations of disease (60 patients each with diabetes for 10 to 19 years, 20 to 29 years, and 30 to 39 years, respectively) were examined for clinical signs of retinopathy, nephropathy, and peripheral neuropathy. The results were compared with the patients' previous and actual smoking habits. Cigarette smoking was defined as daily smoking of at least ten cigarettes for one year or more. Smoking habits of the total diabetic sample were not significantly different from those of a nondiabetic control sample. However, a decline in the number of cigarette smokers and a rising number of ex-smokers were noted with increasing duration of diabetes. In comparing smokers and nonsmokers, no difference was found in the prevalence of peripheral neuropathy, background retinopathy, and proliferative retinopathy. However, the prevalence of nephropathy (persistent proteinuria) was significantly higher (p less than 0.05) among these patients who were or had been cigarette smokers. Thus, cigarette smoking might be considered a risk factor for the development of diabetic nephropathy.