In patients with affective disorders who are being treated with lithium carbonate, lithium concentration is lower in RBCs than in plasma, suggesting an active transport of the ion from the cells (similar to Na+ efflux). Wide variations have been observed in the steady state in vivo distribution of Li+ ratio (defined as intracellular Li concentration/extracellular Li+ concentration), which is under genetic control to some degree.1-3The relationship of this ratio to psychiatric diagnosis, to short- and long-term response to lithium therapy, and to the side effects of Li+ administration has been studied. Preliminary evidence shows that patients with bipolar illness have higher Li+ ratios in vivo than normal controls.4 The finding that patients who respond to lithium therapy have higher Li+ ratios than nonresponders5-7 has not been confirmed by all investigators.8-9Side effects of Li+ therapy may be more highly correlated with intracellular Li + concentrations or the Li+