Abstract--Previous studies demonstrated that a whole-grain diet attenuated sodium-dependent hypertension and renal disease in Dahl salt-sensitive rats from the colony at the Medical College of Wisconsin (Dahl SS/Mcw rats) compared with rats maintained on a purified AIN-76A diet. The present experiments determined which component(s) of the grain diet prevented renal and cardiovascular disease. Male SS/Mcw rats were maintained on isocaloric diets identical to AIN-76A, except the source of protein (wheat gluten for casein), carbohydrate (wheat flour for sucrose), or fat (soybean oil for corn oil) was substituted in separate diets. Rats were maintained on the different diets from weaning and studied after 3 weeks on a high-salt (4.0% NaCl) diet. Substitution of the carbohydrate in the diet did not affect body weight, arterial pressure, or renal disease. Replacement of casein with wheat gluten significantly reduced body weight (258±7 versus 353±3 grams), mean arterial pressure (133±2 versus 153±2 mm Hg), and albumin excretion (9±1 versus 50±7 mg/d) to levels of rats fed the whole-grain diet (n=7 to 16/group). Replacement of the fat in the diet increased arterial pressure without affecting body weight or albumin excretion. The results of the present study indicate that dietary components other than sodium play an important role in the development of hypertension and renal disease in the Dahl SS/Mcw rat.