Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence implicates a "slow virus" infection of the skeleton, perhaps in genetically predisposed individuals. PBD is rare in Asia. We describe a Korean family with PBD. The propositus noticed bowed limbs at approximately 25 years of age. Radiologic studies made when he was 55 years old revealed essentially panostotic PBD. Serum alkaline phosphatase (ALP) activity and osteocalcin (OC) levels were markedly elevated. An iliac crest specimen showed classic histopathologic changes of PBD. Additionally, palpable swellings were first observed at age 45 years at his occiput, pubic ramus, ileum, and facial bones. They contained numerous multinucleated cells and were originally diagnosed as giant cell tumors. However, we found that, like osteoclasts, these cells expressed considerable tartrate-resistant acid phosphatase activity. These "extraskeletal osteoclastomas" resolved rapidly with dexamethasone treatment. Two daughters, 20- and 24-years-of-age, were discovered by study of his 5 children to have elevated serum ALP activity and OC levels and widespread PBD. Both women, however, are without palpable masses and are asymptomatic. The propositus' father, who died at age 55 years, had similar skeletal deformities beginning at age 20 years, but was not examined. Leukocytopenia was found in the 3 living family members with PBD. There was no evidence for linkage of the PBD to HLA loci. The condition appears to be transmitted as an autosomal dominant trait and is manifest in young adult life. Multicentric extraskeletal osteoclastomas with remarkable sensitivity to dexamethasone treatment appear to be another unusual feature of this family's disorder. In this family, the stimulus for PBD is so great that the PBD is apparent at an early age, affects essentially the entire skeleton, and leads to the formation or extension of osteoclast-like cells into nonosseous tissues (extraskeletal osteoclastomas). This 3-generation kindred in Korea, where PBD is rare, shows a strong clustering of PBD compatible with autosomal dominant inheritance. Leukocytopenia appears to distinguish affected family members, but any role for this abnormality in the pathogenesis of PBD is unclear. Our findings support a heritable diathesis for PBD, perhaps mediated by an immune deficiency.