Myelodysplastic syndrome and acute myelogenous leukemia secondary to radiotherapy, radiation exposure, and chemotherapy is a well-documented malignant stem cell disorder. The incidence and natural course of myelodysplastic syndrome and acute myelogenous leukemia after organ transplantation remains less thoroughly investigated. In our institution, 631 heart transplantations have been performed between 1983 and 1998. We report five patients (age, 22-63 years) with myelodysplastic syndrome (MDS) (n=1) or acute myelogenous leukemia (AML) (n=4) occuring 4-8 years after transplantation. Immunosuppression consisted uniformly of a combination of prednisone, cyclosporine, and azathioprine. Successful cytogenetic analysis was performed in three patients, showing typical cytogenetic abnormalities in each case. The course of AML was uniformly fatal. One patient with MDS, refractory anemia with excess of blasts according to the FAB criteria, is alive with transfusion dependency 32 months after diagnosis. MDS and AML may occur during immunosuppression after heart transplantation. Treatment results are poor in this subgroup of patients with secondary leukemia.