The influence of a maintenance diet containing 44.4% dry weight protein and 2 reduced protein diets containing 8.2% and 17.2% dry weight protein on morbidity, mortality, and renal function of dogs with induced chronic renal failure was studied for 40 weeks. The diets differed in mineral and electrolyte composition in addition to differences in protein, carbohydrate, and fat content. Dogs fed the 44.4% protein diet had a higher mortality (6 of 11) than did dogs fed the 8.2% (1 of 6) or 17.2% (0 of 6) protein diets. Dogs fed the 44.4% protein diet died of uremic complications. An occlusive portal vein thrombus caused death of the nonsurvivor fed the 8.2% protein diet. Clinical signs of uremia were detected only in nonsurvivors fed the 44.4% protein diet. Surviving dogs fed the maintenance diet were less active and had poorer hair than did dogs fed reduced protein diets. Inulin clearance rate and urinary protein excretion were lower in most dogs fed reduced protein diets than in dogs fed the maintenance diet. Despite the greater decrease in renal function, serum urea nitrogen concentrations were markedly lower in dogs fed the 8.2% and 17.2% protein diets than in dogs fed the 44.4% protein diet. Seemingly, the reduced protein renal failure diets were of benefit in preventing or reducing morbidity and mortality associated with the uremic syndrome and in reducing serum urea nitrogen concentrations as compared with that of the higher protein diet. The potential benefits of dietary protein restriction in dogs with chronic renal failure prevailed over potential adverse affects of excessive protein consumption.