BACKGROUND: Variations in trace (endogenous) lithium exchanges have been postulated to play a role in the pathophysiology of affective diseases. This prospective study aimed to check whether plasma, erythrocytes and urine trace lithium levels were altered in mood disorders. METHODS: Trace lithium was determined by atomic absorption spectrophotometry in patients without mood stabilizing drugs or somatic diseases, hospitalized for bipolar affective disorders, major depressive episodes, and other psychiatric disorders with depressive features. Patients admitted for psychotic disorders without mood alterations and healthy volunteers served as controls. RESULTS: There were no differences in trace lithium status between the groups. Erythrocytes/plasma ratios appeared higher than described on therapeutic lithium (1.6+/-0.7, N = 199). LIMITATIONS: The study had sufficient power to detect clinically significant differences in whole body lithium handling between the groups. However, it did not address alterations of lithium exchanges across neuronal membranes or the blood-brain barrier. CONCLUSIONS: Alterations of membrane exchanges hypothetically associated with mood disorders are not reflected in plasma or erythrocytes trace lithium levels. The occurrence of mood disorders seems not to be related to abnormalities in endogenous lithium.