We investigated the predictive value of sequential FDG PET before and after high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in 24 patients suffering from non-Hodgkin's lymphoma (NHL). FDG PET was performed at baseline, after three cycles of induction therapy, before and after HDT with ASCT. Response assessment from sequential PET scans using standardized uptake values (SUV) was available in 22 patients at the time of transplantation. Partial metabolic response (PMR) was defined as a >25% decrease of SUV between successive PET scans [corrected]. Six of seven patients who did not achieve a PMR after complete induction therapy developed lymphoma progression, while 10 of 15 patients with complete metabolic response (CMR) or PMR remained in continuous remission. Four of seven patients with less than PMR after induction therapy died vs two of 15 patients with CMR/PMR. Median progression-free and overall survival of patients with less than PMR after HDT and ASCT was 9 and 29 months, respectively. In contrast, neither conventional re-staging nor the International Prognostic Index were predictive. These data suggest that sequential quantitative PET imaging does enlarge the concept of chemosensitivity used to select patients with high-risk NHL for HDT and ASCT or to route them to alternative treatments.