After intracisternal 6-hydroxydopamine (6-OHDA) in mice, brain noradrenaline (NA) and dopamine (DA) are diminished, although the reduction of NA is more pronounced. Intracisternal injection of 6-OHDA in desmethylimipramine (DMI)-pretreated animals strengthens the depletion of DA while NA is partly protected. The concentration of 5-hydroxytryptamine (5-HT) is not influenced by 6-OHDA or 6-OHDA + DMI. Chronic morphine treatment to some extent enhances reduced NA and DA levels after 6-OHDA, but the decreased central catecholamine (CA) content after 6-OHDA + DMI is not raised. Morphine analgesia is highly attenuated in 6-OHDA and 6-OHDA + DMI mice. The reduction occurs in nontolerant as well as in tolerant animals. The acute effect of morphine on body temperature is abolished with 6-OHDA, but not with 6-OHDA + DMI, whereas the interaction of central CA in morphine-induced running shows distinctly marked reduction with 6-OHDA + DMI, but not with 6-OHDA. Acute toxicity is enhanced by 6-OHDA + DMI whereas the development of tolerance against the toxicity of morphine is diminished by 6-OHDA. Lack of CA in the brain decreases sensitivity against naloxone withdrawal in acute as well as in chronic experiments.