Net production or utilization (Qmet) of histidine by the kidney was evaluation or utilization (Qmet) of histidine by the kidney was evaluated in 11 normal and 8 chronically uremic female dogs during intravenous infusion, first of half-normal saline and then an amino acid solution containing L-histidine. Also, Qmet for histidine, alanine, beta-alanine, and carnosine (beta-alanyl-L-histidine) was determined during infusion of half-normal saline and then carnosine into the renal artery in seven normal dogs. During infusion of half-normal saline, Qmet histidine, calculated from the plasma data, was significantly positive in normal but not uremic dogs. Qmet histidine correlated with creatinine clearance. In uremic dogs, plasma histidine was decreased possibly due to decreased renal production and increased urinary excretion. Qmet histidine, calculated from the whole blood data during infusion of half-normal saline, was positive but not significantly so. During carnosine infusion, there was significant utilization of carnosine, and histidine production increased. Thus during fasting, the dog kidney appears to produce histidine, and histidine production increases with carnosine infusion. Hydrolysis of carnosine, possibly by carnosinase, may be a source of histidine released by the dog kidney.