Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell depletion should be restricted to the CD4 subset.