The kidneys are an important factor in controlling the excretion of the sex-dependent protein, alpha 2u globulin, in the urine. On a protein-free diet (0% casein), when the plasma level was reduced by 60%, the daily excretion of alpha 2u in the urine was reduced from a normal of 11 mg to 0.2 mg; 97% of the alpha 2u filtered by the kidneys was reabsorbed. When a normal-protein diet (20% casein) was restored, the serum alpha 2u levels were returned to normal within 48 hours. The urinary excretion, on the other hand, remained below normal until the eighth day after repletion, whereas the renal concentrations of alpha 2u reached higher than normal values by the fourth day. Thus, during protein deficiency the kidney reduced excessive losses of protein in the urine by an almost total reabsorption of alpha 2u. On a high-protein diet (50% casein), the serum levels of alpha 2u were normal, yet its excretion was elevated 80% above the normal (20 mg/day compared with 11 mg/day). To effect this increased loss, the reabsorption of the protein was reduced to 26% of the normal.