Total body potassium decreased after 2 weeks of lithium adminstration in 12 of 13 depressed patients but increased in 6 of 7 manic patients treated with lithium under identical conditions. These opposite changes were statistically significant for each group of patients. In a smaller group of depressed patients followed for longer periods during lithium treatment, the potassium levels returned to prelithium values. The dependence of the direction of potassium change on the clinical state of the patient may be related to some previously described differences between manic and depressed patients and also to differences in the therapeutic response to lithium between the two groups.