Prolonged exposure of rats to cigarette smoke resulted in significant alterations in the metabolism of lipids. There was a significant increase in the concentration of cholesterol, triglycerides and phospholipids in most of the tissues, particularly the heart, aorta and lungs. Cholesterol, triglycerides and phospholipids decreased in the serum HDL and increased in LDL + VLDL. There was increased cholesterogenesis in the heart, lungs and liver, as evidenced by increased activity of HMG-CoA reductase and increased incorporation of labelled acetate into cholesterol. Incorporation of label into the triglycerides also increased in these tissues. Activity of lipoprotein lipase in the extrahepatic tissues was decreased. Activity of glucose-6-phosphate dehydrogenase and malic enzyme increased in the heart and lungs. There was decreased concentration of bile acids in the liver.