In longitudinal and transverse studies, lithium was measured in plasma, serum and red blood cells (erythrocyte) of healthy male and female subjects as well as in patients of both sexes suffering from manic-depressive disease or schizophrenia. The results confirm that lithium in erythrocytes is lower than in plasma in all groups. The lithium concentration gradient between plasma and erythrocytes is not caused by a slow rate of diffusion through the erythrocyte membrane. The new result of the present study is the importance of sex, disease and age on the erythrocyte/plasma lithium ratio, which is significantly higher in female subjects with manic-depressive disease. This difference persists even during long-term lithium therapy. Older female schizophrenics also have a higher ratio of erythrocyte to plasma lithium than males of the same age. The findings emphasize the importance of endocrine investigation in mental disease and support the view that plasma lithium in humans does not always reflect the intracellular levels. The erythrocyte plasma ratio may also be of value in revealing diagnostic subgroups within the classical psychiatric framework.