In the periphery, neuropeptide Y is present in the circulation, in the adrenal medulla as well as at the level of nerve endings and of the juxtaglomerular apparatus. The aim of the present study was to assess the effect of this neuropeptide on renin secretion. Normotensive rats were biadrenalectomized or sham-operated and made hypertensive with methylprednisolone acetate (20 mg/kg s.c. once weekly). Deoxycorticosterone pivalate (10 mg/kg s.c. once weekly) was also given to prevent mineralocorticoid deficiency. Two weeks after that initial surgery 12 adrenalectomized rats and 8 sham-operated rats were infused for 30 min with neuropeptide Y (0.1 microgram/min) whereas 8 adrenalectomized rats and 9 sham-operated rats received in similar conditions the vehicle of neuropeptide Y (10 microliters/min). At that time, the rats were conscious and there was no significant difference in blood pressure and heart rate between the 4 groups of rats. At the end of the experiment, adrenalectomized rats exhibited a markedly stimulated renin-angiotensin system. Neuropeptide Y made it possible to normalize plasma renin activity in these rats, thus suggesting that neuropeptide Y plays an important role in regulating renin secretion.