The present study examined the effect of prolonged morphine treatment on striatal dopamine (DA) release and metabolism, during the initial phase of the development of morphine dependence. Sprague-Dawley rats were implanted with chronic guides for microdialysis of the striatum. Morphine (two 75-mg pellets, subcutaneous implant) or placebo was given (12 hr) to pentobarbital anesthetized animals. Following recovery from anesthesia, morphine physical dependence was verified by the naloxone-evoked abstinence syndrome. Morphine produced significant increases in the dialysate level of DA nad its metabolites (DOPAC and HVA) above baseline compared to placebo treatment. HVA levels began to increase immediately following morphine administration, whereas DA and DOPAC levels began to increase after a latency of one and three hr, respectively. Morphine effects on striatal DA metabolism included changes in the metabolic disposition of DA. Increases in HVA concentration accompanied increases in DOPAC concentration up to a threshold value of DOPAC efflux; further increases in DOPAC level were associated with decreases in HVA level. These in vivo data suggest that morphine-induced changes in the regulation of striatal dopaminergic function may be an important component of the development of physical dependence.