Objective-To determine the extent to which plasma lipid concentrations of individuals are consistently sensitive to changes in saturated fats; to examine whether groups that consistently have large or small responses can be defined; and to identify factors which predict response of lipids to dietary change. Design-A double crossover design in which two diets (S, providing 21% energy from saturated fat, and P, providing 10%) were followed for periods of six weeks in the sequence SPSP or PSPS. Setting-67 free living subjects, total cholesterol 5.5-7.9 mmol/l. Main outcome measures-Relation of cholesterol responses to repeated dietary changes and of potential predictors and cholesterol response. Results Similar average changes in cholesterol mask a wide range of individual responses. Response was not related to compliance. In all participants the change in cholesterol observed when the nature of dietary fat was changed on the two crossovers was correlated (r=0.31, P=0.01); the degree of correlation between the two sets of responses was greater in the 46 consistent responders than in the 21 variable responders (r=0.71 v r=0.21). Mean differences in cholesterol between diet S and diet P during the two crossovers were 1.16 (SD 0.35) mmo/l and 0.95 (0.26) mmol/l for consistent hyperresponders and 0.18 (0.26) mmol/l and 0.18 (0.25) mmol/l for consistent minimal responders. in consistent responders, changes in total cholesterol in response to increasing saturated fats correlated with baseline cholesteryl ester transfer activity (r=0.32, P=0.03); total cholesterol (r=0 37, P=0.01); triglycerides (r=0.30, P=0.04); and apolipoprotein B (r=0.54, P=0.01). Conclusions-There is a degree of consistency in cholesterol response to instructions to change dietary fat which is not explained by dietary compliance, and there are groups of consistent hyperresponders and minimal responders within population of hypercholesterolaemic individuals. Several factors predicting response have been identified. These results have relevance to dietary approaches aimed at reducing the Lipoprotein mediated risk of coronary heart disease.