The effects of exercise training on muscle protein catabolism in uremia were studied in female rats. Rats made uremic by 3/4 nephrectomy were compared with sham-operated control female rats under conditions of exercise training by swimming or no exercise. The release of amino acids from epitrochlearis muscle in vitro was measured. Body weight epitrochlearis muscle weight, and epitrochlearis protein content were similar among groups. Uremia increased the release of phenylalanine and tyrosine 33% and alanine 50% from muscle of sedentary rats. Citrate synthase activity and glycogen content of muscle were increased twofold by exercise in both controls and uremics. Exercise increased the release of alanine (60%), glutamine (50%), and pyruvate (30%) from muscles of control rats, but it decreased to control levels the release of phenylalanine and tyrosine in uremic rats. Alanine release remained elevated. To determine if exercise training increases in vitro muscle sensitivity to insulin, we incubated muscle with and without 0.01 U/ml of insulin. Phenylalanine and tyrosine release was reduced minimally by insulin in both sedentary uremic and control groups. Glucose uptake was enhanced by 55% in both groups. But in the exercised uremic and control groups, insulin reduced phenylalanine and tyrosine release by 50% and increased glucose uptake by 75%. These results suggest that exercise training reduces muscle protein catabolism in uremia; and this reduction is associated with enhanced muscle response to pharmacologic doses of insulin in control and uremic rats.