One hundred twenty-six adult female baboons (Papio cynocephalus) were hysterectomized and all except 18 were ovariectomized. The animals were fed a moderately atherogenic diet (40% calories form hydrogenated vegetable oil, 1.5 gm cholesterol/kcal) for two years. Ovariectomized-hysterectomized animals received estrone sulfate, ethynyl estradiol, or diethylstilbestrol orally in daily doses similar to those given humans. An ovariectomized-hysterectomized group and a hysterectomized group received no drug. The average total serum cholesterol concentration rose from 136 mg/dl to 223 mg/dl and declined to 186 mg/dl. Concentrations of cholesterol, triglyceride, and phospholipid in whole serum, low density lipoproteins and high density lipoproteins showed no consistent statistically significant differences among the groups. Triglyceride and phospholipid concentrations were higher in the estrogen-treated and intact-ovary groups than in the ovariectomized nonestrogen treated group, but not all pairwise comparisons were statistically significant. There were no consistent statistically significant differences in atherosclerotic lesions among the groups. Neither ovariectomy nor estrogen replacement influence diet-induced experimental atherosclerosis in the baboon within two years.