The effects of mu- and delta-opioid receptor activation on sympathoadrenal and cardiovascular responses to stress were examined in conscious rats. The mu-selective agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) or the delta-selective agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) was injected into a lateral cerebral ventricle, then rats were stressed by restraint. Plasma catecholamines were measured, and arterial blood pressure and heart rate were recorded continuously. Restraint stress evoked increases in plasma catecholamines and heart rate in saline-pretreated rats. Both DAGO and DPDPE increased basal plasma levels of catecholamines and blood pressure, and DAGO, 5 nmol, produced bradycardia. DAGO, 5 nmol, but not DPDPE, potentiated the plasma catecholamine responses to restraint. However, the presence of DAGO or DPDPE during restraint resulted in decreases in heart rate and blood pressure. The effects of DAGO and DPDPE on plasma catecholamines, heart rate, and blood pressure were blocked by a mu-selective dose of naloxone but were not reversed by the delta-selective antagonist ICI 174864. These results indicate that mu-receptor stimulation during restraint stress facilitates sympathoadrenal and parasympathetic outflow and results in vasodilatation of some peripheral vascular beds.