The inhibition by naloxone of tolerance and dependence in morphinized mice is dose- and time-dependent. In animals receiving a single, large dose of morphine, partial inhibition by naloxone of the analgesic effect results in partial development of tolerance and dependence. This relationship appears to be true for animals which were treated with morphine chronically. Complete and sustained blockage of morphine receptors by naloxone is required for complete inhibition of the development of tolerance and dependence.