We aimed to assess the effectiveness of cyclophosphamide, etoposide and G-CSF (C+ E) to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma. A matched cohort study was performed comparing patients mobilized with C+ E to patients mobilized with cyclophosphamide and G-CSF (C alone). Patients were matched for disease, prior radiotherapy and a chemotherapy score reflecting the amount and type of prior chemotherapy. Thirty-eight consecutive patients mobilized with C+ E were compared with 38 matched controls. C+ E was equivalent to C alone in terms of numbers of patients achieving a minimum threshold of⩾ 2× 10 6/kg CD34+ cells (82% vs 79%, P= 0.74). C+ E was superior, however, in terms of total CD34+ yield (6.35 vs 3.3× 10 6/kg, P< 0.01), achieving a target graft of⩾ 5× 10 6/kg (55% vs 34%, P= 0.04) and obtaining both a minimum (61% vs 32%, P< 0.01) and target (45% vs 13%, P< 0.01) graft in one apheresis. This superiority was largely confined to patients with lower chemotherapy scores. There was no difference in neutrophil and platelet recovery or transfusion requirements for those who subsequently received high-dose therapy and stem cell transplantation. Thus, C+ E improves the efficiency of peripheral blood stem cell collection, but does not increase the number of patients who can proceed to transplantation. Most of the benefit of the regimen was confined to patients who had not received extensive prior therapy. Novel strategies are required to increase the collection efficiency of ‘hard to mobilize’patients.