1. During a prospective and outpatient study the correlation between the lithium ratio and the incidence of lithium side effects and type of comedications was studied in 51 Iranian bipolar patients by using new direct method of measuring erythrocyte lithium concentration. 2. Results revealed that patients who received lithium alone the incidence of lithium side effects was extremely lower than those with lithium and neuroleptics in combination. Both neurological and renal side effects of lithium were higher in patients who received lithium in combination with neuroleptics. 3. In patients on lithium alone the lithium ratio among patients with side effects were significantly lower than those without side effects, and the plasma lithium concentrations were significantly higher in those with side effects. In patients who received neuroleptics in combination with lithium, the lithium ratios were also significantly lower in those with serious side effects than those with slight side effects, but there were no significant correlation in plasma lithium concentrations between them. 4. Previous studies about the correlation of the lithium ratio and incidence of side effects have yielded inconsistent results, and methodological problems may be a reason for these discrepancies. By using the new direct method of measuring erythrocyte lithium concentration, repetition of previous studies on lithium ratio may elucidate its value as a tool in daily practice.