1. 1. The effect of acute morphine administration on the rotational behavior of unilaterally brain-lesioned mice and on the amphetamine-induced rotational behavior of unilaterally brain-lesioned rats was studied. 2. 2. The effect of repeated morphine administration on the rotational behavior of mice and rats was also investigated. 3. 3. Acute administration of 40 mg/kg of morphine induced strong ipsilateral rotation in unilaterally brain-lesioned mice. 4. 4. One day after withdrawal, mice given morphine repeatedly for 5 days and treated acutely with 40 mg/kg of morphine rotated significantly less ipsilaterally than mice that had received the same dose of morphine for the first time. 5. 5. Rats given 2 mg/kg of morphine 1 hr before administration of 5 mg/kg of amphetamine tended to rotate slightly more in the ipsilateral direction than the similarly lesioned control rats that received amphetamine alone. 6. 6. After 1 day of withdrawal from 5 days of repeated morphine administration, rats given morphine before amphetamine tended to rotate less ipsilaterally than those given morphine before amphetamine for the first time. 7. 7. Thus, repeated administration of morphine appears to induce tolerance to the effect of morphine on circling behavior in unilaterally brain-lesioned mice and rats.