Evidence of active transfer of certain non-electrolytes across the human red cell membrane.

1. Permeability of the human erythrocyte to glycerol, as indicated by the course of hemolysis and volume changes, is depressed by Cu(++), Hg(++), I(2), p-chloromercuribenzoate, and phlorhizin, without effecting general permeability changes. In so far as tested (Cu(++), p-ClHgB), these inhibitors delay exit of glycerol from the cell as well as its entry. 2. Permeability to glucose is similarly depressed by I(2) and phlorhizin, and is extremely sensitive to Hg(++) and p-chloromercuribenzoate, but is not affected by Cu(++). An extensive series of other enzyme poisons is without effect in either system. 3. The effects of the sulfhydryl inhibitors are prevented or reversed in the presence of glutathione, cysteine, etc. 4. The kinetics of the volume changes in glucose-saline solutions indicates a mechanism for transport of glucose into the cell, regulated by the existing intracellular concentration, rather than by simple diffusion gradients. 5. The intermediation of a sulfhydryl group at the cell surface, probably an enzymatic phosphorylation, is suggested as an essential step in the passage of glycerol, glucose, and other like substances, across the human red cell membrane.