We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P less than 0.01) its fractional clearance via the receptor path, but fractional catabolism by the receptor-independent route remained unchanged. Moreover, although the absolute rate of catabolism of the apoprotein was not affected by treatment, the amounts handled by each pathway altered. Catabolism via the physiologically controllable receptor route increased by 71 per cent (P less than 0.05), but there was a 12 per cent drop in clearance by the nonreceptor pathway. These data demonstrate the utility of cholestyramine in promoting low-density-lipoprotein catabolism via its specific physiologic clearance pathway. They also show that heterozygotes with familial hypercholesterolemia can increase the activity of their low-density-lipoprotein receptors when presented with an appropriate stimulus.