The use of major tranquillisers as antidepressants is reviewed and 34 double-blind trials evaluating this were found. Results suggest that some neuroleptics have antidepressant properties, although most studies have been conducted on mixed anxiety-depressive states. Advantages over the tricyclic antidepressants are the early onset of action and relative lack of side-effects. Post psychotic depression following major tranquilliser therapy is considered, and it is concluded that it is likely to be part of the underlying illness and not a drug-induced effect. It is suggested that further work with major tranquillisers in depression may be of value in exploring the mechanism of action of antidepressant drugs.