Over a 9-year period 37 consecutive adults with primary refractory (n = 13) or first relapse of ALL (n = 24) received an intensive salvage chemotherapy regimen with the final intention of undergoing stem cell transplantation (SCT). Twenty-nine patients who achieved complete remission (CR) were assigned to receive autologous SCT (autoSCT) or allogeneic SCT (alloSCT) based on age and availability of a histocompatible sibling. Of the 19 patients assigned to autoSCT, 10 did not reach the transplant due to early relapse (n = 9) or fungal infection (n = 1), and nine were transplanted a median of 2.5 months (1-8) from CR, eight with an immunologically purged graft. One patient died early from ARDS and eight relapsed 2-30 months post-SCT. Three of the 10 patients assigned to alloSCT relapsed early, but all 10 received the assigned transplant a median of 2.5 months (1-7) from CR. Four died from transplant-related complications 0.7-12 months post-SCT, and six are alive and disease-free 9.7-92.6 months after the procedure. In an intention-to-treat analysis, the mean overall survival from CR for those assigned to autoSCT and alloSCT are 11.3 months (0.5-34.3) and 60.1 (2.3-98.3), respectively (log-rank, P < 0.01). Only 65% of patients who reached CR and 51% of the initial 37 cases underwent the intended SCT. We conclude that few adults with refractory or relapsed ALL actually reach SCT in CR even when the protocol used is designed for this purpose. AutoSCT appears to offer little benefit in this setting, and an alloSCT from a related or unrelated donor should be rapidly pursued after achieving CR.