Xanthoma was produced in diet-induced hypercholesterolemic rabbits by intradermal dextran sulfate injections. The serum cholesterol level returned to the normal range at about 10 weeks after ending the cholesterol diet. Gross observations after cessation of the cholesterol diet revealed a decrease in xanthomatous infiltrations. However, the dense foam cell infiltrations and cholesterol accumulations showed no signs of regression at even 9 months after ending the cholesterol diet. Signs of foam cell migration into the blood stream were not observed. The persistence of the xanthoma may be due to a lack of acceptors, such as high-density lipoproteins, that remove the cholesterol from the foam cells. During our 9-month observation period, some foam cells were degenerated and a few were fused with each other to transform into Touton-type giant cells. Nonfoamy histiocytes were infiltrated around these degenerating foam cells. The histiocytes may have transformed into foam cells by incorporating the lipids of the degenerated foam cells.