A reproducible model of nutrient-induced atherosclerosis simulating that observed in humans was developed during preliminary studies in 400 New Zealand albino rabbits. Atherosclerosis was then induced in an additional 1600 rabbits in sets of 40 animals by maintaining plasma cholesterol levels between 1000 and 2000 mg/dl for 6-20 weeks. Ten rabbits in each set were killed to document the severity and distribution of the baseline atherosclerosis, and the remaining 30 rabbits in each set were assigned randomly to one of 3 groups of 10 animals. Group I animals continued to receive the atherogenic diet, Group II animals were given standard laboratory rabbit pellets, and Group III animals were infused continuously with specially formulated anti-cholesterol nutrient solutions via central venous catheters for the next 6 weeks. Complex atherosclerotic lesions involved 85-90% of the aorta in Group I. In Group II, atherosclerosis was comparable with the baseline control group with no regression manifested. In Group III, 90-95% regression of atherosclerosis was consistently documented. Correlations between plasma amino acid levels and plasma cholesterol concentrations of patients with severe atherosclerosis were used to modify the amino acid composition of the solution in order to maximize its cholesterol reducing capacity specifically for each patient. Infusion of the modified total parenteral nutrition solution induced reduction in plasma cholesterol by 40-65% within one week in 30 preliminary study patients. Subsequently, in 12 patients with severe atherosclerosis, total plasma cholesterol levels decreased by 44 ± 1.25% within 10-14 days regardless of the initial cholesterol level. Moreover, clinical and laboratory evidence of arrest and reversal of atherosclerosis, together with significant improvement in cardiovascular function and diminution of adverse signs and symptoms of circulatory incompetence was manifested during and after the 90-day period of i.v. anticholesterol therapy.