Amoxapine, a member of the dibenzoxazepine drugs which includes loxapine, has recently been introduced for the treatment of depression. We present five cases of amoxapine failure after an initial good response, which showed severe deterioration with an increase in dosage. The dopamine-blocking effects of amoxapine metabolites are discussed. The mechanism of failure may be related to either the appearance of akinetic depression or a strong neuroleptic effect.