The acute relationships between the urinary excretion of sodium and water and renal perfusion pressure were characterized in the rat using a new in vivo model of pressure diuresis. Neural and hormonal influences on the kidney were held constant by denervating the kidney and by maintaining fixed high plasma levels of vasopressin, aldosterone, corticosterone, and norepinephrine levels by intravenous infusion. Renal perfusion pressure (RPP) was varied above and below control using specially designed aortic clamps. Increasing RPP within the autoregulatory range from 90 to 160 mmHg produced 5- to 20-fold increases in urine flow and sodium excretion with no detectable changes in glomerular filtration rate, renal blood flow, or peritubular capillary pressure. The slope of the line relating urine flow and RPP averaged 2 microliter X min-1 X kidney-1 X mmHg-1 rise in RPP. If RPP was first lowered to 90 mmHg, urine flow could be doubled by increasing RPP by as little as 5 mmHg. Uninephrectomy 7-12 days before an experiment did not alter the renal pressure diuresis relationship. The presence of intact renal nerves, however, was found to shift the relationship between urine flow and RPP to the right. The magnitude of the response produced by elevations in pressure using this new model of pressure diuresis was greater than when RPP was increased using carotid occlusion or epinephrine infusion as in previous studies. The results indicate that small changes in arterial pressure may have a greater influence on sodium and water excretion than has been previously recognized.