Red blood cells (RBCs) from normal volunteers were incubated in vitro at four different extracellular lithium concentrations. Extracellular lithium concentration affected RBC lithium accumulation in several ways. As extracellular lithium concentration increased, the inter-individual variability of RBC lithium accumulation increased. Furthermore, the ratio of RBC lithium concentration to extracellular lithium concentration (lithium ratio) increased in relation to increasing extracellular lithium concentration. A lack of agreement among the authors of recent reports dealing with the significance of the lithium ratio as a psychobiological measure has been noted. It is suggested that this lack of agreement may be due, in part, to the study of patients with differing levels of extracellular lithium.