Positive assortative mating of baboons (Papio sp.) based on elevation of serum cholesterol concentrations in response to a cholesterol- and saturated fat-enriched diet produced 64 progeny (30 high line; 34 low line). When the animals were 3 to 4 years of age, we tested their lipoprotein cholesterol responses to dietary cholesterol and fat in a factorial experiment with two levels of dietary cholesterol (1.7 and less than 0.01 mg/kcal) and two types of fat, coconut oil (P/S 0.1) and corn oil (P/S 3.5), each providing 40% of total calories from fat; we also tested their responses to chow. The high line animals had significantly higher very low density plus low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) cholesterol levels on all diets. The effects of dietary cholesterol on VLDL + LDL cholesterol concentrations were greater in high line animals than in low line animals, but dietary cholesterol's effects on HDL cholesterol were similar in both lines. The effects of saturated fat, compared to unsaturated fat, on both VLDL + LDL and HDL cholesterol levels were similar in both lines. Selective breeding produced lines diverging in lipoprotein cholesterol concentrations by acting on several different genetically mediated processes that control serum lipoprotein levels. At least one of these processes involves responsiveness of serum VLDL + LDL cholesterol concentration to dietary cholesterol.