This study examined the altered lipid metabolism and effects of drug treatments during the development of adjuvant arthritis in rats. Before its onset (day 9 post-adjuvant), large decreases were noted in the serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels and, in particular, a large decrease in the lecithin-cholesterol acyltransferase activity. A large increase in the serum phospholipid level was also noted. As the arthritis progressed, the serum total cholesterol and HDL-cholesterol levels were rapidly reversed, finally reaching a level significantly higher than normal, together with rises in the serum free-cholesterol and lipid peroxide levels. These changes in serum lipids and enzyme activity could be normalized by treatment with cyclophosphamide, an immunosuppressive agent, but other than the serum triglyceride level, were not affected by treatment with indomethacin, a nonsteroidal anti-inflammatory drug, despite the fact that both drug treatments almost completely suppressed the progression of arthritis. These findings suggest that the abnormal lipid metabolism induced by adjuvant injection is not associated with the inflammatory activity, but associated with the immunopathologic response.