Cigarette smoking was known to promote the progression of diabetic nephropathy in patients with type 1 diabetes, but its influence on the course of diabetic nephropathy in patients with type 2 diabetes had not been previously established. In a prospective follow-up study we therefore compared the progression of nephropathy in type 2 diabetic patients with or without tobacco consumption. Initiation of dialysis treatment or death of the patient were the end points of the study. 36 patients with type 2 diabetes complicated with diabetic nephropathy were included in the study, 16 smoked and 20 did not. The main outcome measures were proteinuria, arterial blood pressure, HbAlc, serum-creatinine and creatinine clearance, which were controlled at least every six months. In the smoking diabetic patients the mean (SD) creatinine-clearance decreased from 82 +/- 10 to 10 +/- 6 ml/min/1.73 m2 over a period of 62 +/- 21 months. The rate of decline of the creatinine-clearance was 1.24 +/- 0.34 ml/min/month. In the non-smoking patients the creatinine-clearance decreased from 79 +/- 8 to 9 +/- 3 ml/min/1.73 m2 within 79 +/- 27 months. The rate of decline in the creatinine-clearance was 0.99 +/- 0.35 ml/min/month (p < 0.025). HbAlc, systolic and diastolic blood pressure as well as serum cholesterol and triglycerides were not significantly different in both patient groups. Therefore, we conclude that cigarette smoking promotes the progression of diabetic nephropathy in patients with type 2 diabetes, just as it is known in type 1 diabetic patients.