Previous studies have shown that the opioid antagonist naloxone does not alter neurotensin (NT)-induced antinociception. In the present studies, tolerance to morphine in mice significantly attenuated NT-induced antinociception, but not NT-induced hypothermia. In addition, centrally administered NT inhibited naloxone-precipitated jumping in morphine-dependent mice. These results indicate complex interactions between NT-induced antinociception and opioid systems.