OBJECTIVE To describe the myelodysplastic syndromes (MDS) and cytogenetic abnormalities that occur in patients who have been treated with alkylating drugs for their rheumatic disease. METHODS Patients with rheumatic disease who developed MDS after current or previous treatment with alkylating drugs were selected for evaluation by chart review and cytogenetic studies. RESULTS Eight patients with rheumatic disease (mean age 56.9 years) developed MDS over the study period. Seven had received oral cyclophosphamide and 1 chlorambucil as their main immunosuppressive drug. The mean total cumulative dose of cyclophosphamide or chlorambucil was 118 gm and 6.5 gm, respectively, over a period of 2-10 years. The cytogenetic abnormalities included a deletion of all or part of chromosome 7 in 5 patients, while 4 had a deletion of part of the long arm of chromosome 5. Six of the patients have since died. CONCLUSIONS Large cumulative doses of cyclophosphamide and chlorambucil were associated with the development of MDS, the occurrence of abnormalities of chromosome 5 and/or chromosome 7 deletions, and a poor prognosis.