Loss of heterozygosity (LOH) or allelic deletion at various loci has been reported in the majority of human tumors. The frequently deleted targets are believed to be tumor suppressor genes. Recent studies have identified the APC and MCC genes at 5q21, as putative tumor suppressor genes. The APC and MCC genes have been implicated in the development of familial adenomatous polyposis coli and cancers of the gastrointestinal tract, ovary, breast and lung. In the present study, we investigated a possible role of the APC and MCC genes in prostate cancer development. mRNA expression of the APC and MCC genes and LOH at the APC and MCC loci were determined in prostate cancer tissues from 28 patients and 5 human prostatic adenocarcinoma cell lines. Of the informative cases, the frequency of LOH at the APC and MCC loci was 63% (10/16) and 54% (7/13), respectively. Overall, 65% (15/23) of the informative cases showed LOH at the APC and/or MCC gene. All prostate cancer cell lines showed homozygosity at all APC and MCC polymorphic sites studied. Approximately half (57%) of the tumor tissues examined showed a decreased expression of APC and MCC mRNA. Our data suggest that the APC and MCC genes may be involved in the formation of human prostate cancer (HPC).