The N-methyl-D-aspartate (NMDA) receptor is implicated in multiple aspects of pain processing by the central nervous system. However, the role of NMDA receptors in the endocrine and autonomic aspects of nociception remains uncertain. The present study examined the influence of the NMDA receptor antagonist, MK-801 (0.02-2.0 mg/kg, intracarotid), on the adrenal and autonomic responses to corneal stimulation (mustard oil, 20% sol.) in barbiturate-anesthetized rats. Fos-like immunoreactivity (Fos-LI) evoked by corneal stimulation was quantified within the spinal trigeminal nucleus (Vsp) of MK-801 pretreated animals to assess activation of central trigeminal neurons. Corneal stimulation-evoked increases in the plasma concentrations of adrenocorticotropin (ACTH), epinephrine and norepinephrine were reduced dose-dependently by MK-801. Plasma ACTH also increased after moderate hemorrhage, a response that was not affected by MK-801. MK-801 did not reduce the magnitude of corneal stimulation-evoked increases in arterial pressure and heart rate; however, prestimulus arterial pressure was reduced by drug treatment. Fos-LI was distributed bimodally within the ipsilateral caudal Vsp: one peak of Fos-LI in the subnucleus interpolaris/caudalis transition region and a second peak within the superficial laminae of the subnucleus caudalis/upper cervical cord transition region. The magnitude of both peaks of Fos-LI was reduced dose-dependently by MK-801. These results indicate a significant contribution from NMDA receptors in control of select endocrine and autonomic responses that accompany trigeminal nociception and in activation of central trigeminal neurons that process corneal nociceptive input.