Human hepatocellular carcinomas (HCC) frequently show loss of heterozygosity at loci on the short arm of chromosome 8. To define a region on 8p commonly deleted in HCC, we used 20 restriction fragment length polymorphism markers to carry out detailed deletion mapping in 142 HCC. Of the 124 informative cases, 56 (45%) showed allelic losses in tumors. While more than half of them had lost alleles at every locus on the short arm, others lost them partially or interstitially. Common deletion of an 8-cM region flanked by cMSR-32 and cC18-245, at 8p21.3-p22, suggested the presence of a tumor suppressor gene(s) in this interval. Correlation between allelic losses on 8p and clinicopathological parameters were examined in the 51 cases for which detailed clinical data were available; allelic losses on 8p were observed in none of five tumors at stage T1 (0%), nine of 20 tumors at stage T2 (45%), and 17 of 26 tumors at stage T3/T4 (65%). A higher frequency of allelic losses on 8p was observed in poorly differentiated tumors (10/14, 71%) than in well differentiated tumors (3/13, 23%). The association of allelic losses on 8p with advanced clinical stage and poor differentiation implies that loss or inactivation of a tumor suppressor gene(s) on 8p may play a role in the progression of HCC.