Two molecular defects have been described in parathyroid adenomas: rearrangement and overexpression of the PRAD1/cyclin D1 oncogene and allelic loss of chromosome 11 DNA, often including the multiple endocrine neoplasia type 1 (MEN1) putative tumor suppressor gene region. In an effort to identify additional parathyroid tumor suppressor genes, we examined 25 parathyroid adenomas for tumor-specific allelic loss of polymorphic DNA loci located near known or candidate tumor suppressor genes. Control leukocyte DNA from all 25 patients was heterozygous for 1 or more of the 9 chromosome 1 markers examined. Allelic loss at 1 or more of these informative loci on chromosome 1 was observed in 10 of 25 (40%) adenomas. Although many tumors lost extensive regions on chromosome 1, all but one of these tumors had allelic loss of distal 1p (1p32-pter); four tumors also lost loci on 1q. Allelic loss at 11q13, the site of the MEN1 gene, was detected in 5 of 21 (24%) informative cases, including 3 with 1p loss. In contrast, allelic loss was rarely observed at loci on 9q and 10p and was not observed at loci on 3p, 3q, 4p, 5q, 12q, 14q, 18q, 22q, or Xp. In summary, clonal allelic loss of loci on chromosome arm 1p is a frequent feature of parathyroid adenomas, implying that inactivation of a tumor suppressor gene(s) on 1p commonly contributes to their pathogenesis.