The influence of pertussis toxin (PTX) injected intracerebroventricularly (i.c.v., 0.5 micrograms) on the analgesic effect induced in the rat by i.c.v. injection of morphine (5 micrograms) was studied. Morphine analgesia was unaffected 24 h after toxin administration, but there was a significant decrease after 6 days. Therefore a PTX-sensitive substrate, probably a guanine nucleotide regulatory protein could be involved in the coupling of opiate receptors to cellular effectors responsible for the expression of the antinociceptive action of morphine.