BRCA1, a breast-ovarian cancer susceptibility gene which has been localized to 17q21, appears to be a tumor suppressor gene based on evidence from loss of heterozygosity (LOH) studies. We analyzed 14 ovarian and breast tumors from BRCA1 carriers and 1 sporadic breast tumor from 3 kindreds for 17q21 LOH. Thirteen of the 14 tumors from gene carriers exhibited LOH of the wild-type allele. Tumors from one gene carrier and the sporadic breast case did not exhibit any LOH in the region. There was loss of the wild-type allele from both maternally and paternally derived chromosomes, therefore excluding the possibility of genomic imprinting and providing further evidence that BRCA1 is a tumor suppressor. Three tumors showed interstitial LOH in the region, and thus established the utility of familial tumors in refining a region surrounding a tumor suppressor gene in a manner analogous to using genetic recombinants.