The in vivo spare receptor population and the relative efficacies of morphine and the endogenous enkephalins to alleviate thermal nociceptive inputs were compared by using the mu irreversible antagonist beta-funaltrexamine (beta-FNA). Twenty-four hours after i.c.v. administration of beta-FNA at increasing concentrations (0.005-2.5 micrograms), parallel rightward shifts of both morphine and RB 101 (mixed enkephalin-degrading-enzyme inhibitor) dose-response curves, were observed, but the concentration of beta-FNA required to reduce the analgesic responses was about 10 times higher for RB 101 (0.1 microgram) than for morphine (0.01 microgram). The preferential involvement of mu receptors in the analgesic responses obtained after beta-FNA pretreatment, was supported by the inability of the delta-selective antagonist naltrindole to block these effects. In conclusion, it seems that to elicit the same antinociceptive responses, enkephalins could occupy a smaller proportion of mu opioid receptors than morphine, suggesting that the endogenous peptides have a higher efficacy.