Aged mice (6 months of age) fed a conventional diet were shifted to diets containing 10% lard, high-linoleate safflower seed oil, high alpha-linolenate perilla seed oil or high-docosahexaenoate fish oil. A significant increase in whole body cholesterol (/g wt) was seen within 30 d after the shift (rapid response), followed by a gradual decrease in 60 to 120 d (slow response); similar changes occurred in all the dietary groups. Shortly after the shift, the serum cholesterol concentrations increased to higher levels in the lard and safflower oil groups than in the other groups, and the levels at 120 d were in the group order of safflower oil > lard > perilla oil > fish oil. Rapid and slow responses to dietary shifts were also seen in hepatic cholesterol levels (/g wt), which were higher in the lard group than in the other groups at 120 d. The arterial cholesterol contents of the fish oil group tended to be less than in the other groups at 120 d. Thus in aged mice after a relatively long-term feeding (> one tenth of the life-span), safflower oil was not hypocholesterolemic as compared with lard and other omega 3-rich oils. Long-term feeding of fish oil maintained serum cholesterol concentrations at lower levels than feeding with safflower oil or lard and without accumulating cholesterol in the aorta, liver or whole body; perilla oil was also hypocholesterolemic but to a lesser degree than fish oil.(ABSTRACT TRUNCATED AT 250 WORDS)