Studies of bupropion in rats, dogs, and normal volunteers showed that bupropion was rapidly and completely absorbed, widely distributed in tissues, and metabolized extensively prior to its excretion. Metabolism in rats and dogs appeared to be predominantly by side chain oxidative cleavage, while reduction of the intact parent aminoketone to an aminoalcohol was an additional major pathway in man. Most of the metabolites were excreted in urine. Bupropion, but not its metabolites, was concentrated in many tissues, with a brain to plasma ratio of about 25:1. Plasma protein binding of bupropion (75%-80%) did not seem to limit its tissue distribution. Bupropion was found to be a weak to moderate inducer of drug metabolism.