To elucidate the fundamental actions of endogenous opioids and naloxone on the cerebral circulation, the effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels were investigated in cats. Pial arteries (165.7 +/- 24.9 microns) were found to dilate after the intravenous administration of 1 mg/kg of (D-Met2,Pro5)-enkephalinamide, and a definite dilatation of 7.1-7.6% persisted for 15 min. Pial veins (100.6 +/- 20.2 microns) also dilated but to a lesser degree. The MABP (118.7 +/- 10.5 mm Hg) decreased by 20 mm Hg immediately after the injection, but gradually returned to the initial value 15 min later. The observed cerebral vasodilatation may be attributable to sympathetic inhibition mediated either by the presynaptic opiate receptors of the cerebral vessels or by the opiate receptors in the brainstem. After the intravenous administration of 1 mg/kg of naloxone, pial arteries (122.0 +/- 17.2 microns) showed a slight but significant dilatation of 2.3-5.3%. There were no significant changes in pial veins (87.0 +/- 12.4 microns). MABP (130.4 +/- 12.3 mm Hg) was slightly increased after the injection. Although the mechanism involved was unclear, the cerebral vasodilatation occurring after the administration of naloxone may contribute to its ameliorating effect on the neurological symptoms following cerebral ischemia.