Despite the fact that follicular lymphomas are both chemo- and radiosensitive, the disease is generally non-curable. These lymphomas often undergo transformation to a more malignant state. In order to improve the prognosis, high-dose treatment with stem cell support has been tested, but its role in the treatment of this disease is still unclear. Fourteen men and eight women with a median age of 45 yr (34-59) were treated with high-dose therapy with autologous stem cell transplantation between 1987 and 1996. The patients were selected to undergo intensive therapy because of an estimated short survival (median < 3 yr), even though they had chemosensitive disease and adequate performance status. Eleven patients' lymphomas had transformed, and the other eleven patients had one or more unfavourable prognostic signs such as advanced stage, bulky disease, multiple relapses, or short remission duration. The conditioning regimen has varied over the period, but BEAC (Becenum, etoposide, cytarabine, cyclophosphamide) or etoposide/cyclophosphamide with or without total body irradiation (TBI) was used in most patients. Nine patients had their stem cells purged. After a median follow-up time of 74 months overall survival was 81% and disease-free survival 72%. One toxic procedure-related death occured. There was no difference in outcome between patients with a transformed lymphoma compared to those without transformation. The patients treated with TBI had a significantly worse outcome. Toxicity was also much higher in TBI-treated patients, including four cases of secondary malignancy (three myelodysplastic syndrome (MDS) cases and one patient with breast carcinoma). This retrospective study, with the longest follow-up time so far reported, shows a promising 6-yr DFS of 72% in a group of follicular lymphoma patients with a bad prognosis. The outcome of patients with transformed lymphoma compared to historical controls is especially encouraging. The high incidence of MDS is worrying. The role of TBI should be questioned because this and other studies have not shown any advantage of using TBI. In the absence of randomised trials the role of high-dose treatment for patients with follicular lymphoma is still not defined.