Effects of dietary histidine and arginine on nitrogen retention were compared in six young men consuming for 1 week, each of six semipurified diets containing eight indispensable amino acids proportioned as in casein and 6.3 g nitrogen daily. Nonspecific nitrogen was either A) a mixture of six dispensable amino acids and arginine (diet 1) or arginine and histidine (diet 2) in casein proportions, or B) an isonitrogenous mixture of glycine and diammonium citrate alone (diet 3), with histidine (diet 4), arginine (diet 5), or histidine and arginine (diet 6). Nitrogen retention was significantly greater when the nonspecific nitrogen source was dispensable amino acids, arginine and histidine (diet 2) than when it was glycine and diammonium citrate (diet 3). mean balances were positive only when diets contained histidine (diets 2, 4, and 6). Histidine with arginine (diets 2 and 6) significantly improved nitrogen retention compared to arginine alone, but the balance, although positive, was not significantly improved when histidine was fed without arginine (diet 4). Urinary urea nitrogen confirmed these data. Indicators of erythrocyte status, plasma enzyme activities and proteins, and creatinine clearance were unaffected by diet. In summary, histidine supplementation of the low nitrogen diet improved total nitrogen utilization when arginine was present in the diet.