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1. The effect of chlorpromazine on hexose transfer across the human erythrocyte membrane was investigated by optical and isotopic techniques in intact erythrocytes.

2. Chlorpromazine produces two phases of inhibition of glucose exit at 17° C in both types of experiment.

3. Glucose exchange flux shows a much smaller decrease in flux rate at the same concentrations of chlorpromazine at 17° C.

4. Sorbose and glucose entry at 36° C show a similarly complex inhibition by chlorpromazine. The inhibitor constant (K_i) for these effects with the two sugars is similar.

5. An Arrhenius plot shows that the average energy change for the reaction of the carrier with chlorpromazine is -46 kJ mole^-1 and suggests that a drug-induced conformational change in the carrier may occur.

6. These findings require models of hexose permeation to contain separate terms in their kinetics for net and exchange fluxes and the predictions of one such model have been compared with the experimental results.