Two incubation procedures were used for the determination, in vitro, of the steady‐state Li+ ratio between red cells and external media. The Li+ ratio in vitra determined prior to Li+ therapy correlates significantly with the subsequent ratio in vivo between red cells and plasma in patients treated with Li+. The Li+ ratio determined in vitro in patients during Li+ therapy was significantly higher than the value determined during the pretreatment, drug‐free period but correlated significantly with Li+ ratios in vivo. The in vitro procedure used thus could be applied in the prediction of the in vivo Li+ ratio, and possibly of the response to Li+, in patients before treatment is begun. It also could be used for studies on abnormalities and on the genetics of Li+ transport in affective illness.