The purpose of this study was to evaluate the efficacy of potentiation of antidepressants with lithium or carbamazepine in the treatment-resistant depression, and to assess the influence of these agents on endocrine parameters and adenosine triphosphatase activity. Variables associated with good outcome were also ana1ysed. Fifty nine patients with treatment-resistant depression were randomly allocated to addition of either lithium or carbamazepine to ongoing treatment. Efficacy of both strategies was similar in the group of treatment-resistant patients. In the lithium group, decrease in cortisol level in responders and increase in nonresponders were observed. These observations may suggest regulatory influence of lithium on the hypothalamus-pituitary-adrenal (HPA) axis activity in patients with good results of lithium potentiation. CBZ responders had significantly lower baseline severity of depression than CBZ nonresponders. Clinical improvement correlated significantly with increase in adenosine triphosphatase activity in that group.