Longterm cytotoxic therapy, particularly with alkylating agents, is frequently associated with the development of second neoplasms, particularly acute myeloid leukemia. Twelve patients with classic, progressive rheumatoid arthritis (RA), treated with a cytotoxic agent, cyclophosphamide, from 1969 to 1974 at the University of Colorado Health Sciences Center were reassessed for current status of the granulocytic system. Bone marrow biopsies were investigated histologically and the number of granulocyte precursor cells judged using colony forming cells in culture (CFU-C). Control bone marrow biopsies were done on 8 patients with classic, progressive RA who had not taken cyclophosphamide as well as 16 healthy controls. Colony forming cell numbers in patients with RA who had been treated with cyclophosphamide were significantly lower compared to patients with RA who had not received cyclophosphamide and normal controls. These data suggest that cyclophosphamide may cause suppression of the hematopoietic system that does not totally recover even after long periods of time.