Thirty-four patients with tricyclic-resistant depressive illness took part in a nine-week, double-blind, placebo-controlled trial of lithium augmentation. In addition to the maximum tolerated doses of their tricyclic antidepressant, the experimental group (n = 16) received 250 mg lithium daily for three weeks, followed by 750 mg lithium daily for six weeks, while the controls (n = 18) received placebo for three weeks followed by three weeks each of 250 mg lithium daily and 750 mg lithium daily. There was no significant difference between placebo and 250 mg lithium for weeks 0-3 of the trial. However, there was a significantly greater improvement on the MADRS for weeks 3-6 for those subjects on 750 mg lithium than for those on 250 mg lithium. In addition, using a 50% fall in the HRSD as a criterion of drug responsiveness, 22% responded to placebo, 18% to 250 mg lithium, and 44% to 750 mg lithium. Thus, lithium in normal, but not in low, dose has a significant antidepressant effect in TCA-resistant depression. Further controlled studies using lithium in normal dose in trials which have a greater duration of placebo exposure are required to confirm the lithium augmentation effect.