The present experimental study was planned to evaluate the effect of intrathecal administration of L-glutamic acid upon antinociception produced by intrathecal morphine in a prospective-controlled manner in conscious freely mobile Sprague-Dawley albino rats. After chronic catheterization of the spinal subarachnoid space, rats were randomly allocated into 12 treatment groups of ten each and the same number of rats served as saline control for the comparison. L-glutamic acid (100 mmol), morphine (1.2 mmol), ketamine (50 mmol) and saline (150 mmol) were injected intrathecally in 5 microliters volumes. Naloxone was injected in a dose of 1 mg.kg-1 im. Immediately before and 15, 30 min, 1, 2 and 3 hr after injection, rats were subjected to a thermal noxious stimulus, using a tail-flick technoanalgesiometer and tail-flick latencies (TFL) were recorded. Intrathecal administration of L-glutamic acid attenuated the antinociceptive effect of intrathecal morphine with a decrease in TFL (1.4 +/- 0.3 sec; P < 0.0001) from 6.6 +/- 0.3 sec. Ketamine led to abolition of this effect (P < 0.01). In rats, pretreated with naloxone, there was restoration as well as augmentation of morphine-induced antinociception in the presence of L-glutamic acid with an increase in TFL (9.0 +/- 0.4 sec; P < 0.0001). We conclude that there is modulation of opioid receptors by L-glutamic acid at the spinal site in rats.