The influence of blockade of endogenous opioids on the release of renin due to partial renal arterial constriction was determined acutely and chronically in unilaterally nephrectomized dogs. In acute preparations changes in plasma renin activity, arterial blood pressure, and heart rate were determined after 15 min of 60% renal arterial constriction before and after administration of either a saline vehicle, the opiate antagonist naloxone (0.05 mg/kg), or morphine (2 mg/kg). Acute antagonism of endogenous opiates abolished the increase in plasma renin activity and mean arterial pressure associated with renal arterial constriction. Repeated renal arterial constrictions in saline- or morphine-treated animals did not alter the humoral or hemodynamic responses. In chronic preparations long-term naloxone infusion attenuated the development of renovascular hypertension and diminished the increase in plasma renin activity. These data suggest that endogenous opioid peptides are modulators in the control of renin release and may be important participants in the pathogenesis of hypertension.