Morphine antagonized d-amphetamine circling in rats which had received unilateral 6-OHDA lesions of the striatum but failed to reduce the circling in rats with both a unilateral 6-OHDA striatal lesion and a raphe (5-HT) lesion. Naloxone precipitated withdrawal of morphine tolerant rats greatly enhanced d-amphetamine circling when the rats had a 6-OHDA lesion but not when both 6-OHDA and raphe lesions were present. It is concluded that 5-HT is necessary for the morphine-induced inhibition of the circling. The effect of morphine tolerance and naloxone precipitated withdrawal on brain 5-HT function was investigated using a putative 5-HT rotation model in which both a dopamine and a 5-HT agonist were administered to rats with an asymmetrical medial raphe lesion. The findings suggest that chronic treatment with morphine increases striatal 5-HT function.