The frequency of ischaemic heart disease observed after splenectomy for trauma and the low cholesterol levels found in patients with hypersplenism are observations that suggest a possible role for the spleen in lipid metabolism and in the aetiology of atherosclerosis. The present study was designed to examine this role in experimental animals. Serum levels of total cholesterol, triglyceride and high-density lipoprotein (HDL) cholesterol were determined in 32 rats. The spleen was removed in 16 rats and the remaining 16 were sham operated. Half of the splenectomized and half of the remaining rats were fed on a diet rich in fat and the two other subgroups were fed normal chow. Blood tests were performed before, and 3 and 6 months after operation. A significant increase in serum triglyceride and decrease in serum HDL cholesterol levels was observed after splenectomy in rats fed normal chow compared with sham-operated rats. An increase in serum triglyceride and a decrease in serum HDL cholesterol levels was observed in both groups of rats fed normal chow plus high-fat cheese. However, these changes were more pronounced in splenectomized rats. These findings suggest that the spleen has a role in lipid metabolism in rats and may therefore influence atherosclerosis.