In rats, microinjection of the opioid agonist morphine (15-45 nmol/0.5 microliter) and the excitatory amino acid monosodium glutamate (30-60 nmol/0.5 microliter) into identical brainstem sites within the mesencephalic periaqueductal gray matter (PAG; 23 sites) and the rostral ventromedial medulla (RVM; 22 sites) produced an increase of tail flick and hot plate response latencies. At both PAG and RVM sites, there was a statistically significant relationship between the effect obtained with morphine and with glutamate on the two nociceptive responses. While morphine and glutamate produced indistinguishable inhibition of tail flick and hot plate response latencies in the PAG, the tail flick inhibition following RVM morphine, but not RVM glutamate, displayed a clear plateau. One parsimonious interpretation of these data is that (1) glutamate directly increases the activity in the bulbospinal pathway, and (2) morphine inhibits an evoked or tonic suppression of a bulbospinal projection.