The effect of chlorpromazine (CPZ) and a number of CNS depressant drugs on glucose penetration through human erythrocyte membrane has been investigated by an optical technique. CPZ accelerated glucose exit at concentrations between 1 × 10 −5 and 2 × 10 −5 M at 36° but at higher concentrations inhibited transfer. This inhibition was rapidly and completely reversible. CPZ, trifluoperazine, prochlorperazine, promazine and promethazine were found to inhibit glucose exit approximately in the order of their chemotherapeutic potency. Imipramine also showed this effect but nealbarbitone, thiopentone and haloperidol did not. CPZ affects the entry of glucose into erythrocytes in a biphasic manner similar to its effect on exit but at all concentrations it accelerates the penetration of ethylidene glucose which enters by diffusion. CPZ had no effect on the inhibition of glucose transfer produced by incubation with dinitrofluorobenzene (DNFB) or on the enhancement of this inhibition by incubation in the presence of glucose and 2-deoxyglucose. It is suggested that at low concentrations CPZ accelerates the movement of the glucose carrier within the membrane by effects on its charge environment. At higher concentrations interaction with the protein of both membrane and carrier presumably causes interference with carrier movement until at high concentrations haemolysis occurs. The relevance of these effects to the pharmacological action of CPZ is discussed.