In the periphery, neuropeptide Y is present in plasma, in the adrenal medulla as well as in sympathetic nerve endings and in the juxtaglomerular apparatus. The aim of the present study was to assess the effect of this peptide on renin secretion. Normotensive rats were adrenalectomized 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 initial surgery, 12 adrenalectomized and 8 sham-operated conscious rats were infused for 30 min with neuropeptide Y (0.1 micrograms/min) whereas 8 other adrenalectomized and 9 sham-operated conscious rats received under similar conditions the vehicle of neuropeptide Y (10 microliter/min). Neither before nor during the infusions was there a significant difference in blood pressure and heart rate between the 4 groups of animals. Plasma renin activity, measured at the end of the infusion, was 30.5 ng/ml/hr in the adrenalectomized group receiving vehicle and 6.3 ng/ml/hr in that infused with neuropeptide Y (p less than 0.001). This latter value did not differ from that found in sham-operated rats. These results suggest that neuropeptide Y may play an important role in regulating renin secretion.