Twenty-nine African green monkeys were fed diets for 22 months containing 0.79 mg cholesterol/kcal and 40% of calories as either safflower oil or butter with or without the addition of an estrogen- and progestin-containing oral contraceptive. Plasma cholesterol concentrations ranged from 199 to 250 mg/dl. Animals consuming the safflower oil diet had plasma cholesterol concentrations that averaged 61 mg/dl lower than those consuming butter. At least 72% of this lowering was due to a reduction in low density lipoproteins. Triglyceride concentrations were also slightly lower in animals consuming the safflower oil diet. The oral contraceptive lowered total plasma cholesterol concentrations in both diet groups by an average of 41 mg/dl with 54% of this lowering (22 mg/dl) due to a reduction in high density lipoprotein cholesterol. This effect occurred only during the 3 weeks while the contraceptive was being administered and was not apparent 1 week after stopping the drug. Animals consuming safflower oil had bile that was more lithogenic and had more gallstones than did those consuming butter. Addition of the oral contraceptive caused a slight increase in bile lithogenicity, but this increase was not statistically significant. There was no significant interaction between the oral contraceptive and either of the diets to exacerbate cholelithiasis. At the plasma cholesterol concentrations achieved only minimal amounts of atherosclerosis developed and there were no indications of differences due to diet or oral contraceptive in the extent of atherosclerosis.