To evaluate the clinical impact of minimal residual disease in multiple myeloma, apheretic products from 51 autotransplanted patients were tested by fluorescent (GeneScan) polymerase chain reaction (PCR). Sixty-nine per cent of harvests were contaminated when evaluated for IgH rearrangement. Forty-six patients responded to transplant, with 52.9% achieving complete response (CR). The clinical response of patients was significantly influenced by the number of re-infused CD34+ cells. Positive PCR results of re-infused harvests were not significantly related to patient outcome. Median overall survival (OS) was 33 months, and a significant advantage for patients transplanted by 12 months from diagnosis was observed. Moreover, OS was longer for patients receiving PCR-negative stem cells, with 72% of patients surviving to 70 months in the group receiving PCR-negative harvests vs 48% in the group transplanted with contaminated precursors (not statistically significant). Ex vivo purging caused a reduction of contamination of up to 3 logs; nevertheless, 80% of purged harvests remained PCR-positive and the purging procedure did not alter response or survival rates. Thus, the failure of a predictive role for this highly sensitive molecular method could be explained by the assumption that in vivo persisting malignant cells are the true source of relapse in MM.