This study assessed nonfasting cholesterol and triglyceride in plasma and in lipoproteins as predictors of the extent of aortic atherosclerosis in 2 similar groups of rabbits from the St. Thomas's Hospital strain; the lipoprotein classes studied in the 2 groups were very low (VLDL), intermediate (IDL), low (LDL), and high density lipoprotein (HDL), and Sf greater than 60 lipoprotein, Sf 12-60 lipoprotein, LDL and HDL, respectively. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL, with plasma cholesterol and triglyceride of up to 23 mmol/l and 7 mmol/l, respectively, and with up to 100% of the aortic intima bearing atherosclerosis-like lesions. In group 1 rabbits (n = 25), univariate linear regression showed that cholesterol in plasma, LDL, IDL and in VLDL each were positively associated with the extent of aortic atherosclerosis. In group 2 rabbits (n = 20), cholesterol in plasma, LDL and Sf 12-60, but not in Sf greater than 60 lipoprotein, was consistently positively associated with the extent of aortic atherosclerosis. Neither plasma triglyceride, triglyceride in lipoprotein fractions nor HDL cholesterol was associated consistently with the extent of atherosclerosis. Using step-up multiple linear regression among lipoprotein lipids, IDL and Sf 12-60 lipoprotein cholesterol were the most powerful independent predictors of the extent of aortic atherosclerosis in the 2 groups of rabbits. LDL cholesterol was the only other independent predictor. The results suggest that remnant lipoproteins, whether defined as IDL or Sf 12-60 lipoprotein, play an important causal role in atherosclerosis under conditions where plasma levels of these lipoproteins are elevated.