Modulation of the spinal nociceptive tail flick (TF) reflex by electrical stimulation of subdiaphragmatic or cervical vagal afferent fibers was characterized in rats lightly anesthetized with pentobarbital. Cervical vagal afferent stimulation (VAS) inhibited the TF reflex in a pulse width-, frequency-, and intensity-dependent fashion. The optimum parameters for inhibition of the TF reflex were determined to be 2.0 ms pulse width, 20 Hz frequency with a threshold (T) current of 60 microA. Cervical VAS at 0.2-0.6 T facilitated the TF reflex. Cervical VAS at T typically produced a depressor arterial blood pressure response, but inhibition of the TF reflex by VAS was not due to changes in blood pressure. Subdiaphragmatic VAS also inhibited the TF reflex and generally produced a pressor effect, but did not facilitate the TF reflex at intensities of stimulation less than T as did cervical VAS. The parameters of cervical VAS required for inhibition of TF reflex suggest that excitation of high-threshold, unmyelinated fibers are important in VAS-induced descending inhibition. The intrathecal administration of pharmacologic receptor antagonists into the subarachnoid space of the lumbar enlargement indicated that the opioid receptor antagonist naloxone produced a dose-dependent antagonism of cervical VAS-produced inhibition of TF reflex, but single doses of either phentolamine or methysergide (30 micrograms each) failed to affect the inhibition by VAS. Combined intrathecal injection of both phentolamine and methysergide (30 micrograms each), however, significantly attenuated inhibition of the TF reflex by cervical VAS. These results suggest that cervical VAS engages a spinal opioid system and co-activates descending serotonergic and noradrenergic systems to modulate spinal nociceptive processing.