Liver regeneration after partial hepatectomy is accompanied by altered hepatic intermediary metabolism. Because the organochlorine compound mirex also causes liver cell growth, the purpose of this study was to investigate hepatic carbohydrate and oxygen metabolism in perfused livers from mirex-treated rats and to localize cell proliferation in this model. Pretreatment with mirex (100 mg/kg, intragastrically) increased liver/body weight ratios and DNA synthesis in livers of fed rats, effects that were markedly diminished in livers of fasted rats. This finding shows that liver growth caused by mirex, as is the case after partial hepatectomy, is hindered when animals are deprived of food. Furthermore, perfused livers from mirex-treated rats had depleted glycogen stores but significantly elevated oxygen uptake compared with livers from control rats. Increases in oxygen uptake and hepatocellular proliferation were observed mostly in periportal regions of the liver lobule. In regenerating livers, most DNA synthesis was reported to also occur in these regions of the liver lobule. Taken together, these data show that liver cell growth caused by mirex is accompanied by changes in hepatic intermediary metabolism and sublobular proliferation similar to those observed after partial hepatectomy.