1. The cholesterol and phospholipid content of the cell membrane and the efflux of sodium were measured in the erythrocytes of patients with chronic cholestasis and in healthy subjects.
2. The membranes from the patients contained more cholesterol and phospholipid and had a higher cholesterol/phospholipid molar ratio than the membranes from the healthy subjects.
3. The sodium efflux rate constant was reduced in the patients and this was entirely due to a reduction in the frusemide-sensitive efflux rate constant. There was no difference in either the ouabain-sensitive or the ouabain plus frusemide-resistant rate constants.
4. This reduction in the frusemide-sensitive rate constant was associated with a reduction in the erythrocyte sodium content.
5. When erythrocytes were loaded with cholesterol in vitro the frusemide-sensitive efflux rate constant was reduced by an amount similar to that observed in the patients. In addition, however, there was a reduction in the ouabain-sensitive efflux rate constant and an increase in the erythrocyte sodium content; neither of these changes was observed in the patients in vivo.