A family is described in which three members, the propositus, his brother, and son, developed a myelodysplastic syndrome (MDS) at the ages of 52, 35, and 25, respectively. A fourth member, the paternal uncle of the propositus, was diagnosed with chronic lymphocytic leukemia. Two of the three affected Individuals had megaloblastoid marrows with recognizable bone marrow cytogenetic abnormalities and progressive, nonleukemic bone marrow failure. The propositus was unresponsive to G-CSF and eventually died of sepsis. The second affected family member died of bone marrow transplant complications. The third affected family member underwent bone marrow transplantation and is showing signs of graft survival despite minor complications. The affected members of this pedigree appear to represent a continuum in severity of disease and, therefore, pathogenesis. The pattern of inheritance and clinical progression of the disease suggest a genetic defect which may predispose individuals to the development of MDS.