The authors studied the effect of codeine on 12 severely depressed patients who failed to respond to tricyclic antidepressants. They all were in involution. Eight patients received codeine in combination with other tricyclic antidepressants and only one of them showed improvement. Four depressed patients received codeine alone and none of them improved. The patients were kept on codeine up to three weeks. The dose was gradually increased from 90 mg/day to 180 mg/day. All patients suffered from severe constipation--more than what they had on tricyclic antidepressant medication. All of the patients experienced a sedative effect. None of them had euphoria and none of them developed dependence. After the failure of codeine, the patients finally accepted electroconvulsive therapy or monoamine oxidase inhibitors, and with one exception, all improved.