The changes in systolic blood pressure, plasma renin activity (PRA), and sodium balance were studied during the first 3 weeks of the development of renal hypertension in rats with an undisturbed contralateral kidney. Moderate hypertension (160 to 180 mm Hg) was reached after application of a 0.25-mm solid clip; severe hypertension (200 to 230 mm Hg) developed after application of a 0.20-mm solid clip. Basal levels of PRA in peripheral blood increased only in rats with a 0.20-mm clip, when blood pressure had already risen to 160 to 180 mm Hg. Elevated peripheral PRA, however, may have contributed to the initial increase of blood pressure in both groups of hypertensive rats, as indicated by higher late-afternoon PRA values at the peak of the normal diurnal rhythm of PRA. PRA in renal venous blood from the clipped kidney increased during the development of both moderate and severe hypertension at a rate quantitatively related to the rise in blood pressure. During the first 8 to 10 days after application of both sizes of clips, sodium retention per gram gain in body weight was significantly higher than in the sham-operated controls. Subsequently, sodium balance and blood pressure stabilized in animals with a 0.25-mm clip. In the rats with a 0.20-mm clip, sodium balance returned to control levels and became even lower than in the sham-operated group. Despite this negative sodium balance, blood pressure showed a further rise. These results suggest that in rats with an undisturbed contralateral kidney, a positive sodium balance has a role in the early phase of the development of renal hypertension. The enhanced plasma renin activity also probably contributes to the early phase, but appears to make a major contribution to the further development of severe hypertension.