Background and Aim: The effect of lowering serum cholesterol by means of a cholesterol-binding resin on human red cell membrane cholesterol and fluorescence polarisation anisotropy was assessed in 16 subjects with primary hypercholesterolaemia. Methods and Results: After 3 months of lipid-lowering therapy there was a significant reduction in serum cholesterol, with a concomitant small increase in serum triglycerides. Membrane cholesterol levels and fluorescence polarisation anisotropy of 1,6-diphenylhexatriene (DPH) and 1-{(4-trimethylamino)-phenyl}-6-phenylhexatriene (TMA-DPH) were all reduced significantly. No changes occurred in 8 normolipidaemic subjects studied at 0 and 3 months without treatment. There was a negative correlation between serum triglycerides and DPH anisotropy, but no correlation between serum and membrane cholesterol, nor between membrane cholesterol and membrane anisotropy. Despite differences in serum cholesterol levels, membrane cholesterol levels and membrane anisotrophy were similar in the two study groups. Conclusions: These results suggest that membrane cholesterol content is maintained within narrow limits. Increased membrane fluidity may be associated with the lowering of membrane fluidity may be associated with the lowering of membrane cholesterol content. However, serum triglycerides appear to be more strongly associated with membrane fluidity than serum cholesterol. (C) 1996, Medikal Press.