This study examined effects of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), on facilitation of the tail flick reflex (1) by intrathecal administration of 6.5 nmol of substance P at the lumbar spinal level in awake rats and (2) by noxious cutaneous stimulation in anesthetized rats (by immersing the tip of the tail in hot water at 55 +/- 1 degrees C for 1.5 min). Reaction time was decreased by about 70% by intrathecal administration of substance P and by about 40% by tail immersion. Intrathecal administration of APV (2 nmol) or cerebrospinal fluid (CSF) failed to alter the baseline responses. However, APV but not CSF blocked the facilitation induced by intrathecal administration of substance P and by tail immersion. These results indicate that while NMDA receptors do not appear to be involved in mediating the tail flick reflex, they may be involved in expression of the facilitation of this reflex by substance P and/or by a related peptide.