This study was performed in order to examine the influence of tobacco smoking on carbohydrate and lipid metabolism and microangiopathy in diabetic patients with normal serum creatinine. Among 163 adult insulin-treated patients 114 smoked daily (smokers). Compared with nonsmokers, smokers had on the average a 15–20% higher insulin requirement (P < 0.001) and serum triglyceride concentration (P < 0.05), increasing to a 30% rise in heavy smokers (P < 0.01). The degree of retinopathy was equal in the two groups, as was the average creatinine clearance [99 ± 2 (mean ± 1 SEM) versus 101 ± 4 ml/min in smokers compared with nonsmokers]. Smokers and nonsmokers were comparable regarding sex ratio, age at diabetic onset, duration of diabetes, residual beta-cell function, fasting hyperglycemia, and glycosuria. Evidently, tobacco smoking represents a strain on both carbohydrate and lipid metabolism in insulin-treated diabetes mellitus.