Multiple myeloma (MM) is characterized by the expansion of tumor plasma cells in bone marrow (BM), but neoplastic cells have been consistently detected in peripheral blood (PB). Peripheral blood progenitor cell (PBPC) collections have been widely used to support high-dose therapy for MM patients. A flow cytometric technique has been used to detect plasma cells in PB and PBPC harvests. High CD38 expression identified these cells, and their nature was confirmed by the coexpression of specific antigens, such as CD138 and cytoplasmic immunoglobulins. Malignant plasma cell reinfusion could negatively affect response rate and survival, as demonstrated in other hematological malignancies. To address this issue, the relationship between the number of reinfused plasma cells, response to chemotherapy and event-free survival (EFS) have been analyzed. Sixty-four MM patients were treated with intensified chemotherapy at diagnosis. They were mobilized with cyclophosphamide and G-CSF, and then treated with melphalan 100 mg/m2 (MEL100) followed by PBPC support. A second course was given after 2 months, and a third to patients not in complete remission. There was no correlation between the number of reinfused plasma cells and response rate after this intensified chemotherapy: patients attaining complete remission received 3.6 x 106/kg CD38+ cells, while those with a partial or no response received 5.6 and 2.9 x 106/kg CD38+ cells. Similarly, there was no correlation between the number of reinfused plasma cells and EFS. Patients receiving less than 4.85 x 106/kg CD38+ cells experienced a median EFS of 34.2 months as opposed to 36.4 months for those receiving more than 4.85 x 106/kg CD38+ cells (P = 0.7). Recurrence of the disease is consistently observed in MM: our data suggest that in vivo residual tumor cells, rather than reinfused plasma cells are more likely to be responsible for relapse. Bone Marrow Transplantation (2000) 25, 25-29.