The effect of methamphetamine on morphine-dependent mice was investigated by calculating the LD-50 (IP), measuring motor activity, anorectic actions, and body temperature. 2. Methamphetamine was more toxic in morphine-dependent mice (LD-50=20.6 mg/kg) than in normal mice (LD-50=43.2 mg/kg). 3. Methamphetamine-induced locomotor activity was greater in morphinized than in nonmorphinized mice at doses of 2.5 and 5 mg/kg IP. 4. Methamphetamine also increased the body temperature of morphinized mice more than that of normal mice (P lt 0.05). 5. These findings suggest that methamphetamine is more toxic in morphine-dependent than in non-dependent mice.