Loss of heterozygosity (LOH) on chromosomes 3p and 9p has been documented in a variety of malignancies, which suggests the presence of tumor suppressor gene loci on these chromosomes. We have studied 77 oral carcinomas for LOH using 16 microsatellite markers distributed over 5 human chromosomes. Fifty-five (71%) of these tumors showed LOH at one or more loci. A significant proportion of LOH at the informative tumors was observed at chromosomes 3p and 9p: 58% and 48%, respectively. A majority of the tumors showed losses at multiple loci on chromosomes 3p or 9p or on both. Our results suggest that tumor suppressor genes located on the short arms of chromosomes 3 and 9 may be involved in the pathogenesis of oral carcinoma. These regions of deletion observed in oral cancers overlap those reported in other neoplasms. However, we did not find any evidence of these changes in tumor margins with early pathological changes.