beta-Blockers are known to slow the progression of diabetic nephropathy by lowering arterial pressure. Moreover, in individuals with diabetic nephropathy, antihypertensive agents that provide sustained reductions in proteinuria slow the rate of decline in renal function compared with agents without this antiproteinuric effect. To examine whether differential effects on proteinuria affect the progression of diabetic nephropathy, we conducted a randomized study that compared the effects of a heart rate-lowering calcium channel blocker, sustained-release verapamil, with those of a beta-blocker, atenolol, on the progression of diabetic renal disease. The primary end point of the study was a change in creatinine clearance slope. Thirty-four African Americans with the following inclusion criteria were randomized to one of the two groups: serum creatinine greater than 1.4 mg/dL, proteinuria greater than 1500 mg/d, longer than a 5-year history of both non-insulin-dependent diabetes mellitus and hypertension, and exclusion of other renal diseases. Goal blood pressure was less than 140/90 mm Hg. All subjects received loop diuretics as second line agents to help achieve the blood pressure goal. Twenty-four-hour urinary protein and sodium excretions as well as creatinine clearance were measured at 6-month intervals. Blood pressure was measured every 3 months. After a mean follow-up of 54 +/- 6 months, the calcium channel blocker group demonstrated both a slower rate of decline in creatinine clearance (-1.7 +/- 0.9 versus -3.7 +/- 1.4 mL/min per year per 1.73 m2, P < .01) and a greater reduction in proteinuria compared with the atenolol group. Additionally, a greater proportion of the atenolol group had a 50% or more increase in serum creatinine compared with the verapamil group (32 +/- 9% versus 16 +/- 7%, P < .05). These between-group differences could not be explained by differences in blood pressure control. These data support the concept that antihypertensive agents that persistently maintain reductions in both arterial pressure and proteinuria slow the progression of diabetic renal disease in African Americans to a greater extent than those agents without these effects. (Hypertension. 1997;29:744-750.)