The effects of supplementation of methionine to a 20% soy protein isolate diet on serum level of cholesterol. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, cholesterol 7 alpha-hydroxylase activity, and biliary and fecal steroids in rats with or without receiving polychlorinated biphenyls (PCB) were investigated. Supplementation of methionine and PCB did not affect the growth. Serum level of cholesterol was higher in rats fed PCB than in controls. In rats fed PCB, addition of methionine elevated serum level of cholesterol synergistically. The activity of HMG-CoA reductase was higher in rats fed the methionine-supplemented diet than in those fed the unsupplemented diet when PCB was included in the diets. Cholesterol 7 alpha-hydroxylase activity (nmol/h.100 g body weight) was higher in rats fed PCB than in controls. Biliary secretion of bile acids was higher in rats fed PCB than in controls. On the other hand, fecal excretion of bile acids decreased in PCB-treated rats, but total steroids were not affected by PCB. In rats fed PCB, the addition of methionine did not alter cholesterol 7 alpha-hydroxylase activity and biliary and fecal steroid output. The data suggest that the increase in serum level of cholesterol due to dietary addition of methionine together with PCB would be mediated through the stimulation of hepatic synthesis of cholesterol.