Summary.-The in vitro metabolisms of [14C]7,12 -dimethylbenz(a)anthracene (DMBA) by post-mitochondrial supernates and microsomes from intact and regenerating rat livers were compared. Both cell fractions from regenerating livers at 48, 72, and 96 h after partial hepatectomy metabolized less [14C]DMBA than similar fractions from intact livers. Prior in vivo treatment with DMBA enhanced metabolism by the cell fractions from both groups, but specific activities of cell fractions from regenerating livers were always about 60% or less of those from intact livers. Thinlayer chromatographic analysis of metabolites formed in incubations using either cell fraction failed to reveal distinct differences between ether-soluble or water-soluble products of similar fractions from intact and regenerating livers. However, highly reproducible differences were found between chromatograms of water-soluble metabolites formed by microsomes and post-mitochondrial supernates in both intact and regenerating livers. Extrapolations from these studies indicate large differences in the metabolic capacity of intact and regenerating livers when expressed on a whole-liver basis, but it is suggested that there may be additional factors contributing to the increased retention of DMBA by regenerating livers.ACTIVELY dividing cells are more sensitive to chemical carcinogenesis than are non-dividing cells (Warwick, 1971;Weisburger and Williams, 1975). For example, regenerating rodent liver is more susceptible than intact liver to tumour induction by 7,12-dimethylbenz-(a)anthracene (DMBA) (Pound, 1968;Marquardt, Sternberg and Philips, 1970) and other chemical carcinogens (Chernozemski and Warwick, 1970;Craddock, 1973), but the reasons for this vulnerability are not known with certainty. In a comparison of [3H]DMBA uptake and persistence in intact and regenerating liver, we found that unmetabolized DMBA persisted at high levels in nuclei and other fractions from regenerating liver, but rapidly disappeared from intact liver; preliminary experiments demonstrated that hepatic microsomes from DMBAtreated partially hepatectomized animals metabolized less [14C]DMBA in vitro than did microsomes from DMBA-treated intact animals (Tomsak and Cook, 1975).We now report a more detailed quantitative comparison of DMBA metabolism, using microsomes and post-mitochondrial supernates prepared from intact and regenerating livers, and also report comparative analyses of DMBA metabolites, using thin-layer chromatography as a screening technique.