In isolated blood-perfused canine kidneys, progressive increases in renal blood flow and its fractional distribution to the inner cortex were correlated with increases in perfusate concentrations of a prostaglandin E-like (PGE-like) substance. The ratio of blood flow to the outer and inner halves of the renal cortex measured by the radioactive-microsphere method changed from 77:23 to 68:32 ( P < 0.001) after 90 minutes of perfusion; simultaneously, the concentration of the PGE-like substance increased from 0.04 ng/ml to 0.59 ng/ml ( P < 0.02). Thus, the greatest rate of increase in the concentration of the PGE-like substance occurred coincidently with the largest increase in inner cortical blood flow, i.e., from 30 ml/min to 69 ml/min ( P < 0.001). During the two subsequent 90-minute perfusion periods, the ratio of outer cortical blood flow to inner cortical blood flow fell to 61:39, and the concentration of the PGE-like substance increased further. When indomethacin was added to the perfusate, the concentration of the PGE-like substance decreased from 1.00 ng/ml to 0.24 ng/ml ( P < 0.05), and renal blood flow decreased, especially in the inner cortex where the decline was from 34% to 19% of total renal blood flow ( P < 0.05). Thus, renal blood flow was redistributed after indomethacin was administered. PGE 2 was infused to determine whether substitution for the loss of circulating PGE-like substance could prevent the effects of indomethacin on the distribution of renal blood flow. Despite administration of exogenous PGE 2 , renal blood flow redistributed after administration of indomethacin, and the ratio of outer cortical blood flow to inner cortical blood flow increased from 68:32 to 80:20 ( P < 0.05). These results suggest that the intrarenal site of synthesis and release of PGE 2 determines its action as a local hormone affecting deep cortical blood flow.