A mother and son with acro-osteolysis (Hajdu-Cheney syndrome) are described. In addition to osteolysis of the distal phalanges, these patients have a generalized osseous dysplasia with osteoporosis, premature loss of teeth, short stature and a distinctive facial appearance. In one of the cases an enlarged sella turcica was associated with no abnormality of endocrine function. A biopsy specimen taken from an area of active osteolysis in a phalanx was studied by light and electron microscopy. There was active replacement of central medullary bone by a fibrous and angiomatous process characterized by the presence of small, thick-walled vessels and an unusual number of interspersed nerve fibers and mast cells. A neurovascular dysfunction with local release of osteolytic mediators may be involved in the pathogenesis of the disorder, but the nature of the osteolytic factor is unknown.