Therapeutic drug monitoring for antidepressants is problematic because the blood concentration is usually poorly correlated with the dose. We have developed a simple method to simultaneously determine the pharmacokinetics of amoxapine (AMX) and its active metabolites 7-hydroxyamoxapine (7-OHAMX) and 8-hydroxyamoxapine (8-OHAMX). Using this method, we studied the pharmacokinetics of AMX and its metabolites in six male and six female healthy volunteers. The subjects received 25-mg and 50-mg single doses of AMX. After each dose, the pharmacokinetic parameters were determined according to their serum concentration-time curves. The area-under-the-curve value for 8-OHAMX was three to five times greater than that for AMX. Serum concentrations of AMX and 8-OHAMX 12 hours after administration were closely associated with the doses of AMX per body weight. This association was even more apparent when AMX and 8-OHAMX were combined. Consequently, AMX may be a useful marker for therapeutic drug monitoring, although the pharmacologic action attributable to its active metabolites should be taken into account.