Previous studies paying attention to concurrent use of lithium (Li+) with a neuroleptic were not done under constant and controlled conditions. We were therefore encouraged to do a prospectively controlled study, presuming constant relevant factors, on concomitant use of Li+ with neuroleptic as well as other psychotropic agents. 2. The effects of concurrent administration of chlorpromazine, haloperidol, imipramine and carbamazepine with Li+ on the erythrocyte:plasma Li+ ratio and the intraerythrocyte Li+ concentration were studied in mice by using a new, direct method of measuring erythrocyte Li+ concentration. 3. All of the foregoing agents with the exception of carbamazepine were observed to significantly decrease the Li+ ratio. 4. Lack of any significant effect by carbamazepine on Li+ transport may be an indication of this drug's efficacy as a supplement in Li+ therapy of bipolar affective disorders. 5. The decrease in Li+ ratio observed with chlorpromazine, haloperidol and imipramine may be explained through the mechanism by which these drugs stabilize the cell membrane and consequently affect Li+ transport in erythrocytes. 6. Moreover, our study proves that, although the Li(+)-sodium countertransport mechanism does not exist in mice, the same interaction between Li+ and other psychotropic drugs is seen. It can be concluded that such interaction is not mediated through Li(+)-sodium countertransport. 7. It is suggested that, with concurrent use of a psychotropic drug and Li+, the amount of intraerythrocyte Li+ concentration be measured, instead of relying on the plasma Li+ concentration alone.
