Fifty-four patients with noninsulin-dependent diabetes mellitus, who had established nephropathy, were examined to evaluate the risk factors for the progression of diabetic nephropathy. Time-averaged values of blood pressure, serum total cholesterol and fasting plasma glucose concentrations, and the degree of proteinuria during their follow-up period (4.2 +/- 0.5 years) were calculated. The correlation between these values and the slope of the regression line for the reciprocal of serum creatinine concentration over time, as an index of the speed of the progression of nephropathy, was examined. Age (61 +/- 1 years), mean arterial pressure (109 +/- 1 mm Hg), and the degree of the proteinureia (2.1 +/- 0.1 in dipstick test) were correlated with the slope. Effects of hypercholesterolemia and smoking on the slope were also examined. Mean arterial pressure was correlated with the slope significantly in patients without hypercholesterolemia (p < 0.05) and there was a tendency bewteen these two in smokers (p < 0.06), while was no correlation found in patients with hypercholesterolemia or in nonsmokers. In addition, the relation between the slope and mean arterial pressure was relatively stronger in smokers without hypercholesterolemia than in nonsmokers with hypercholesterolemia. Our data suggest that blood pressure control as well as smoking avoidance may be important in preventing the progression of noninsulin-dependent diabetic nephropathy.