To assess the usefulness of 4-hydroperoxycyclophosphamide (4-HC) and VP-16-213 (VP-16) as a purging agent for myeloma cells in bone marrow (BM) ex vivo, myeloma cell lines (SK-RCS-1, RPMI-8226), lymphoma cell line (SK-DHL-2) and normal BM cells were treated at different concentrations of 4-HC or VP-16. Clonogenic tumor cells from all three cell lines could be reduced by more than 4 logs, when treated alone or as a mixture with irradiated normal BM cells at a 4-HC concentration of 60 microM. Under similar conditions, approximately 1% of the normal BM myeloid progenitor granulocyte-macrophage colony-forming cells survived. These observations support the use of 4-HC for purging myeloma cells for autologous BM transplantation.