Few systematic data are available on the range of individual blood lipid responsiveness to specific diet changes. Multiple, carefully standardized total serum cholesterol (TC) measurements were made in 58 men under a variety of controlled dietary conditions. Responsiveness was defined for each individual as the change in mean TC per unit change in Diet Score based on the Keys-Minnesota equation. Only 3% were potentially 'nonresponders', and even these probably evidenced some response. Of the group, 64% responded with 30% of prediction. We classed 9% as hyporesponders, while in another 9% responsiveness exceeded 1.5 times expectation. We conclude that in metabolically normal individuals the variation in short-term response to dietary change is normally distributed but that nonresponse to diet change is rare. Because metabolic, intrinsic hyporesponsiveness of TC to change in diet composition is uncommon, assessment of the real effectiveness of a dietary regimen in an individual is best based on observed dietary changes. TC changes among individuals under treatment should be based on multiple determinations and interpreted with caution.