The purpose of the study was to assess the impact of number of salvage regimens needed to demonstrate chemotherapy sensitivity on relapse rates, survival, and toxicity following high-dose therapy and autologous bone marrow transplantation (ABMT) in relapsed or refractory non-Hodgkin's lymphoma. We retrospectively reviewed 136 patients with intermediate-grade lymphoma who underwent ABMT. All patients were treated with salvage therapy to maximum tumor reduction. Three quarters (102/136) of the patients received one salvage regimen, while 31 (23%) patients received two or more regimens. When compared to patients requiring >or= two regimens, patients requiring only one salvage regimen to demonstrate chemosensitivity were more likely to have a longer previous CR from initial therapy (CR >or=12 months in 47% vs 26%; P = 0.04) and to have attained CR with salvage (54% vs 16%; P = 0.001). Both median relapse-free survival (RFS) and overall survival (OS) have not yet been reached in patients receiving one salvage regimen (median follow-up 50.6 months). This is superior to the median RFS of 9.1 months (P = 0.004) and OS of 11.1 months in patients requiring >or=two regimens to demonstrate chemosensitivity (P = 0.002). Time to engraftment, toxic deaths and incidence of myelodysplasia were similar in the groups. The survival rate observed in patients requiring >or=two salvage regimens, although inferior to that of patients receiving a single salvage regimen, are still generally superior to results in the literature for patients treated with chemotherapy alone without ABMT. We conclude that high-dose therapy with ABMT is appropriate for lymphoma patients even when disease reduction requires repeated numbers of salvage regimens.