The relation between clonogenic myeloma cells, assayed in vitro, and clinical status was studied in 20 patients with multiple myeloma before and after VAMP therapy (vincristine, doxorubicin, and methylprednisolone). 14 patients showed an improvement in clinical status, as judged by a fall in myeloma protein and a decrease in plasmacytoid myeloma cell infiltration in the bone marrow. However, in 11 of these 14, there was an increase in the number of clonogenic myeloma cells. This suggests that the treatment changed the myeloma cell population in the residual bone marrow. To be effective, subsequent chemotherapy should be aimed at destroying this population of myeloma cells.