In preclinical studies, the toxicologic profile of bupropion was determined in laboratory animals using exaggerated doses of drug in a variety of toxicologic assays. Under overdose conditions, clinical signs primarily referable to the central nervous system were seen in rats, mice, rabbits, and dogs. Very mild, reversible hepatotoxicity and anemia occurred in dogs with chronic dosing; lifetime administration in rats caused hepatocellular hypertrophy and focal hepatic hyperplasia. In both rats and dogs, there was an increase in liver weight related to hepatic enzyme induction. Appropriate tests indicated that bupropion is unlikely to have the potential to cause teratogenic, mutagenic, or carcinogenic effects in man.