The degree of serum cholesterol lowering by up to almost maximal inhibition of cholesterol absorption was tested during neomycin and neomycin + sitostanol treatment in six hypercholesterolemic men. Neomycin decreased cholesterol absorption efficiency by 49% and the combination by 79%, and serum cholesterol level by 27% and 36%, respectively. The correlation between the absorption percentage and low density lipoprotein (LDL) cholesterol was significant (r = 0.510), and the regression equation (y = 0.04x + 2.59) suggested that the mean LDL cholesterol content would be about 2.5 mmol/l at zero cholesterol absorption. In conclusion, in hypercholesterolemic subjects, the lowering of LDL cholesterol appears to be limited to a low normal range only by almost totally inhibiting cholesterol absorption.