1. Autoregulation of renal plasma flow, by which flow remains constant despite changes in perfusion pressure, was studied in the isolated, perfused kidney of the rat. 2. Autoregulation did not occur in preparations perfused with a protein-free medium consisting of a balanced ionic solution resembling rat plasma in which 3% polyvinylpyrrolidone replaced the plasma proteins, changes in perfusion pressure over the normal autoregulatory range 100-150 mmHg produced a corresponding and linear change in venous outflow and no consistent change in renal vascular resistance. 3. Addition of human serum (5%, v/v) to the medium restored autoregulation; changes in perfusion pressure in the range 100-150 mmHg resulted in a stable plasma flow and a linear change in renal vascular resistance. The addition of bovine serum albumin (3 g/1.) to the protein-free medium restored autoregulation to a similar degree. 4. In kidneys perfused with the protein-free medium, the sensitivity of the renal vasculature to the vasoconstrictor drugs epinephrine and angiotensin II was only 1/40 the level seen in those kidneys perfused with media containing serum or albumin. 5. The experiments show that in the isolated, perfused kidney, autoregulation of plasma flow is not dependent on the presence of the globulin, angiotensinogen, in the perfusion medium; and suggest that failure of autoregulation in kidneys perfused with a protein-free medium could be attributed to the rapid decline in the sensitivity of the vascular smooth muscle to constrictor stimuli.