The effect of changes in dietary cholesterol and fat on serum lipids was studied in 32 healthy men (mean age = 24.8 years). Subjects were fed a controlled diet for 10 days providing 42 to 45% of the total calories from fat, a P/S ratio of 0.3 to 0.5 and two eggs per day. During the next eight weeks, 16 subjects received each of the following diets for four weeks in a crossover design: 1) a control diet with two eggs per day or 2) the control diet with eggs replaced by a cholesterol-free egg substitute. The remaining 16 subjects received each of the following diets in a similar crossover design: 1) a modified-fat diet containing 35% of the total calories from fat, a P/S ratio greater than or equal to 1.0 and two eggs per day or 2) the same modified-fat diet with the egg substitute replacing the eggs. The two-week cycle of menus repeated throughout the study included a wide variety of foods commonly consumed in this country. Although the response of individual subjects varied, analysis of variance showed a significant decrease in serum total cholesterol related to replacement of eggs with the egg substitute and to modification in the type and amount of dietary fat. A significant diet-treatment interaction or sequencing effect was not found. Change in cholesterol intake related to addition or deletion of two eggs in the daily diet had no significant effect on serum triglycerides, high density lipoprotein cholesterol, or relative lipoprotein concentrations.