Whether variability in the efflux of Li from erythrocytes [RBC] may be a marker for manic-depressive disorder in related individuals was examined. The subjects of the study were 73 individuals from 12 families in which there was more than 1 bipolar manic-depressive member. Using an in vitro procedure, RBC were subjected to 4 conditions which are believed to inhibit Li efflux. Only phloretin, an inhibitor of Na+-Li+ countertransport, produced significant inhibition. Variability in this inhibition was not related to the presence or absence of manic-depressive disorder, although it was related to family membership. The implications of these findings are discussed.