Nephrotoxic agents such as puromycin aminonucleoside (PAN) and sodium maleate (MAL) have been used to induce experimental glomerular proteinuria and tubular disease, respectively. Current studies show that PAN caused a massive loss of albumin in the urine while not affecting the excretion of the smaller, sex-dependent α2u-globulin. On the other hand, MAL which inhibits the reabsorption of proteins, increased the loss of both α2u and albumin. Both nephrotoxic agents increased the excretion of albumin when administered to female rats. MAL-induced proteinuria was used as a direct measure of the renal load for α2u and albumin. Renal loads and excretion of α2u and albumin were measured in male rats maintained on 0, 20, and 50% casein diets. On the protein-free diet, the excretion of both α2u and albumin was reduced (less than 1 mg daily); their renal loads were almost totally reabsorbed. On a 50% casein diet the reabsorption of α2u was reduced from a normal of 60% to 10% of the renal load. Thus, the high protein diet increased the excretion of α2u while having little effect on the excretion of albumin. We suggest that dietary protein exerts two levels of control on the excretion of protein in the urine of the adult male rat. Protein-deficient diets stimulate the general reabsorption of proteins thereby minimizing the excretion of α2u and albumin. High protein diets appear to reduce selectively the reabsorption of α2u -globulin, thereby increasing its excretion in t