People's cholesterol levels vary greatly in response to diet, with some of this variation being attributable to genes. Identical twins have exact copies of each others' genes, and by comparing the similarity in their cholesterol response to different diets, can provide evidence for the involvement of genes. This can be done without necessarily having to identify the specific genes involved. Of course, being identical, the twins may also share similar lifestyles and environment that could also affect their dietary response. However, choosing identical twins that differ substantially in lifestyle should lessen these nongenetic effects. Modern genetic studies seek to find an association between dietary responses and differences in specific genes. The trouble is that this approach requires that the relevant genes must be first identified and measured. Twin studies have the advantage of providing a global test of a genetic effect without the difficulty of identifying the important genes. The current study examines the effects of switching from a high-fat, low-carbohydrate diet to a low-fat, high-carbohydrate diet in identical twins. We designed the study to minimize the effects of the twins' shared environment by deliberately choosing twins with divergent lifestyles: one physically active, and the other sedentary. Originally, we had sought to recruit fifty twin pairs into the study, but found that few twins met our requirements of being discordant in their physical activity levels, not using medications that might affect their cholesterol, levels not smoking, and willing to abstain from alcohol, and follow a prescribed diet for twelve weeks. We succeeded in recruiting twenty-nine pairs of male identical twins discordant in their physical activity levels among running-magazine subscribers and participants in foot races. Twenty-eight of these pairs completed the study. On average, the running twins ran 31 miles per week more than the sedentary twins. One-half of the twin pairs were required to follow our prescribed low-fat, high-carbohydrate diet for the first six weeks (20% of total calories as fat, 65% as carbohydrates) and then switch to a high-fat, low-carbohydrate diet (40% fat, 45% carbohydrates) during the next six weeks. The other half of the twin pairs was required to adhere to these two diets in the opposite order.