The antihypertensive action of renomedullary autotransplantation was investigated in rats with unilateral hereditary hydronephrosis showing extensive destruction of the medulla of the affected kidney. All rats were divided into three groups and unilaterally nephrectomized. The first group consisted of rats with a normal kidney remaining. The second and third groups had the hydronephrotic kidney remaining and received renomedullary and renocortical autotransplants, respectively. After completion of baseline studies, all rats were given 1 per cent saline solution instead of drinking water, and relevant parameters were re-examined 14 days later. Significant increase in blood pressure (greater than 150 mm. Hg), extracellular fluid volume, and plasma volume were found in group 3 while no changes were detected in groups 1 and 2. After administration of aspirin (and presumed blockade of prostaglandin synthesis) significant increases in plasma and extracellular fluid volumes were detected in groups 1 and 2, but no change in blood pressure was found. The results show that renomedullary transplantation protects against salt-induced hypertension and further indicate that the renomedullary prostaglandins are not a likely mediator of the antihypertensive action of the renal medulla.