High-dose chemotherapy and autologous stem cell transplantation (SCT) have limited success in patients with refractory aggressive lymphoma. Allogeneic SCT may offer some advantage in this setting by providing graft-versus-lymphoma effect, but the relapse risk remains substantial. In this study, we evaluated the safety and efficacy of rituximab administration after SCT in patients at high-risk for post-transplant relapse, in order to reduce relapse risk. Twenty-eight patients were included with the intent to treat them with rituximab after autologous (n = 16) or allogeneic (n = 12) SCT. Twenty-four were given rituximab starting a median of 47 d post SCT. Three died of SCT complications prior to therapy. Nine patients not achieving a complete remission (CR) post SCT converted to CR with rituximab and with the onset of graft-versus-host disease (GVHD) in three. With a median follow-up of 12 months (range, 3-33 months) the estimated 2-year overall survival and disease-free survival was 85 +/- 7% and 55 +/- 13% respectively. When only those patients who were actually treated are analysed, these rates were 95 +/- 7% and 64 +/- 13% respectively. The relapse risk was 35 +/- 14%. Seven patients had recurrent neutropenia episodes associated with severe hypogammaglobulinaemia, which were further prevented with intravenous immunoglobulin. None of the 10 allogeneic SCT recipients treated with rituximab had severe GVHD. Rituximab may be an effective adjuvant therapy after SCT to reduce the relapse rate and improve the outcome in high-risk aggressive lymphoma. Larger scale comparative trials are necessary to better define its role in SCT.