In contrast to hepatic hydrosteroid dehydrogenases (HSDs) of the aldo-keto reductase family (AKR1C), little is known about a stomach one. From a mouse stomach cDNA library, we isolated two clones encoding proteins of 323 amino acid residues. They exhibited 93.2% amino acid sequence identity and 64-68% with any known HSDs. Recombinant proteins expressed in Escherichia coli reduced 9,10-phenanthraquinone with NAD(P)H as cofactor. The mRNAs were exclusively expressed in stomach, liver and ileum, The present study demonstrates that these proteins are new members of the HSD subfamily and they are named AKR1C12 and AKR1C13, Immunohistochemical analysis suggests that they are involved in detoxification of xenobiotics in the stomach. (C) 1999 Federation of European Biochemical Societies.