Because allelotype analysis of tumors has been important in the identification of new tumor suppressor genes, here we studied loss of heterozygosity (LOH) in a well-defined animal experimental system. We analyzed spontaneous liver tumors from C3HHc x C57BL/6J (B6C3F1) mice and urethane-induced hepatocellular tumors from (C3H/He x Mus spretus) x C57BL/6JBy (HSB) interspecific mice. A total of 95 different genetic markers were tested: 13 in 24 B6C3F1 tumors, 76 in 58 HSB tumors, and six in both groups. Minisatellite finger-printing analysis detected one case of LOH and less than 1% genomic rearrangements in polymorphic and nonpolymorphic bands, respectively. There were no changes at hepatocellular susceptibility loci or at markers homologous to loci frequently lost in human hepatocellular carcinomas. Therefore, our results suggest that LOH and genomic rearrangements are uncommon in mouse hepatocellular tumors.