We examined the effects of breast and formula feeding during infancy on the serum lipoproteins and on atherosclerosis in young adult baboons. Baboons were breast-fed (n = 13) or formula-fed (n = 32) until weaning at 16 weeks of age and thereafter they were fed a diet containing 1.7 mg cholesterol/kcal and 40% of calories as lard until 5 years of age. At 12 weeks of age, breast-fed baboons had higher serum high density lipoprotein cholesterol concentration (HDL-C, 68 vs. 51 mg/dl), lower serum triglyceride concentration (37 vs. 68 mg/dl), and lower very low density plus low density lipoprotein cholesterol (VLDL + LDL-C) to HDL-C ratio (0.65 vs. 0.98) than formula-fed infants. From weaning to 92 weeks of age, breast-fed baboons had a lower serum triglyceride concentration (23 vs. 38 mg/dl) than formula-fed baboons. After weaning, the VLDL + LDL-C/HDL-C ratio increased from 0.65 to 1.0 in breast-fed baboons, but decreased from 0.98 to 0.72 in formula-fed baboons. From 92 to 246 weeks of age, the VLDL + LDL-C/HDL-C ratio was consistently higher in breast-fed baboons compared to formula-fed baboons. At 5 years of age, baboons breast-fed as infants had a greater percentage of intimal surface area involved with atherosclerosis in the abdominal aorta, the iliac-femoral artery, the aortic arch, the brachial artery, and the carotid artery, than did those formula-fed as infants. The greater prevalence of lesions in breast-fed baboons was explained mainly by the higher VLDL + LDL-C/HDL-C ratio.