Between June 1981 and August 1986, 183 patients with the referring diagnosis of aplastic anemia were evaluated with cytogenetic studies and marrow biopsies. Seven patients (4%) on biopsy were found to have myelodysplasia. Seven of the 176 patients (4%) with marrow biopsies that confirmed the pathologic diagnosis of severe aplastic anemia were found to have clonal cytogenetic abnormalities in unstimulated marrow samples. Among the 169 patients with typical aplastic anemia and no cytogenetic abnormalities, 5 (3%) subsequently developed either myelodysplasia or leukemia. Two of three patients with pathologically confirmed aplastic anemia and clonal cytogenetic abnormalities, who were not transplanted, developed myelodysplasia. These results demonstrate that approximately 4% of patients with aplastic anemia have clonal cytogenetic abnormalities of marrow cells, and that while all patients with aplastic anemia may have some risk of developing leukemia, those with a cytogenetic abnormality have an especially high risk.