The effect of bilateral 6-hydroxdopamine (with desipramine) lesions of the ventral tegmental area-substantia nigra region on analgesia produced by morphine and D-amphetamine was examined with the formalin and tail flick tests in rats. These lesions depleted dopamine, but not noradrenaline, in the ventral and anterior striatum. Morphine and D-amphetamine produced analgesia in the formalin test in sham lesioned rats but not in lesioned rats. In contrast, morphine produced the same degree of analgesia in the tail flick test in sham lesioned and lesioned rats while D-amphetamine did not produce analgesia in this test. These data suggest that morphine and D-amphetamine analgesia in the formalin test involves dopamine, whereas morphine analgesia in the tail flick test does not.