To find out whether alkali treated proteins possess nephrotoxic properties, feeding studies were conducted with drastically treated soybean protein and casein, and also with lysinoalanine (LAL), the amino acid known to be formed in proteins subjected to high pH at an elevated temperature. The feeding of synthesized LAL to rats at dietary levels of 100 ppm and above induced typical renal changes, called nephrocytomegalia. No such changes or any other indications of toxicity were observed, however, upon feeding much higher levels of LAL (up to 6,000 ppm) when provided as the protein bound compound in alkali treated casein or soybean protein. When set free by complete acid hydrolysis, LAL induced considerable renal activity, comparable to that of the synthetic compound. These results indicate that alkali treatment of proteins does not induce nephrotoxic properties provided that the compound remains protein bound. Some nephrotoxic activity was observed, however, with peptide bound LAL in break down products (molecular weight < 5,000) of alkali treated casein, but considerably less than that of the free compound. LAL analyses in blood, urine, and feces of rats fed free or protein bound LAL indicated a positive correlation between intestinal absorption and nephrotoxic potential. No renal changes were encountered upon feeding diets with 1,000 ppm synthetic LAL to mice, hamsters, rabbits, quail, dogs or monkeys, which suggest a species specificity of LAL induced renal changes in rats. Chemicals/CAS: lysinoalanine, 18810-04-3, 23250-50-2; protein, 67254-75-5; Caseins; Dipeptides; Vegetable Proteins