In a double-blind crossover study comparing lithium carbonate with desimipramine in the treatment of selected depressed patients, there was considerable improvement in both groups of patients, with no statistically significant difference between the effectiveness of the two drugs. This finding, together with other reports, raises the question of whether lithium carbonate might be effective in the treatment of selected depressed patients. Consideration is also given to the implications of our observations and findings for the bipolar concept of mania and depression. Evidence is considered for an alternative model which highlights some of the similarities between these two clinical states.