The purpose of this study was to examine if morphine, a drug of abuse, exerts site-specific effects on intracranial self-stimulation (ICSS). Rats, implanted with dorsal brainstem (DB) and hypothalamic (HYP) electrodes, bar-pressed for ICSS at two current intensities eight hours a day during six days each of predrug saline, morphine (2.5, 5.0, 7.5 or 10.0 mg/kg) and postdrug saline conditions. There were three patterns of drug effects: “pure” depressions, “pure” facilitations and a biphasic pattern (depressions followed by facilitations). Repeated morphine administration modified the temporal patterning of these effects: shortened duration of depressions and produced earlier onsets of facilitations. Within an animal, DB electrodes displayed more depressions than the HYP electrodes. Tolerance to the depressant effects, observed frequently, occurred occasionally to the facilitative effects of morphine. The drug effects on ICSS were dissociated from those observed on other behavioral measures, and thus are not artifacts of concomitant changes in activity levels.