Some investigators have postulated a synergistic analgesic effect of local anesthetic agents and opiates when given intrathecally or epidurally, but little objective evidence has been presented to quantitate such an effect. A study was therefore undertaken to compare in mice the antinociceptive effects of intrathecal injections of mixtures of morphine with bupivacaine or lidocaine with the effects of these agents when administered alone. The antinociceptive effects (tail-flick and hotp-late tests) of morphine (0.1-1.6 micrograms) with either bupivacaine, 25 micrograms, or lidocaine, 200 micrograms, were significantly greater than the effects of morphine or the local anesthetics when administered alone. When morphine was administered with the local anesthetics, the intensity and the duration of antinociception were greater, although the time courses of the effects resembled that of morphine administered alone. An enhanced effect was also observed when combinations of local anesthetics and low doses of morphine were used that by themselves had no or little effect. The addition of morphine did not affect the motor block produced by the local anesthetics. The results indicate a potentiating effect of local anesthetics on spinal morphine antinociception, a finding that may have important clinical implications.