Nalbuphine (0.1-200 micrograms), unlike morphine (0.1-10 micrograms) administered intrathecally had no effect on the tail flick or hot plate response latencies. In contrast, both intrathecal nalbuphine and morphine inhibited, in a monotonic, dose dependent fashion, the writhing evoked by intraperitoneally administered acetic acid (ED50 = 38 nmol and 1.12 nmol, respectively.) The effects of intrathecal nalbuphine and morphine was antagonized by an equal dose of naloxone administered systemically. Co-intrathecal administration of morphine and nalbuphine revealed that a maximum inhibition of writhing could be obtained with low doses of either drug, while the effects of higher doses of either drug were attenuated as compared to the effects produced by the high dose of either drug alone. These data are consistent with the suggestion that nalbuphine exerts its agonistic effect through a mechanism that is pharmacologically distinct from that of morphine, and the likelihood of two populations of opioid receptors associated with the pain response evoked by thermal and visceral afferents, respectively is considered.