Neuropeptide Y is known to enhance blood pressure responsiveness to various constrictors, including angiotensin II, and to suppress renin secretion. This study was undertaken to assess the effect of neuropeptide Y on the development of two-kidney, one clip renal hypertension. Normotensive rats either had a silver clip placed on the left renal artery or were sham-operated upon. An osmotic minipump, which was connected via a catheter to a jugular vein, was implanted subcutaneously in all rats. These pumps delivered either neuropeptide Y (0.001 microgram/min) or saline intravenously. Eight days later, an intra-arterial catheter was inserted and the rats were studied while not anesthetized on the following day. Neuropeptide Y did not affect body weight. In clipped rats, neuropeptide Y prevented the development of hypertension and suppressed renin secretion. Neuropeptide Y significantly decreased blood pressure also in sham-operated rats, although it had no effect on plasma renin activity. These data indicate that prolonged neuropeptide Y infusion may lower blood pressure by different mechanisms, one of which is probably a suppression of renin release.