The standard treatment for patients with aggressive B-cell lymphoma--particularly diffuse large-B-cell lymphoma [DLBCL)--is cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP) plus rituximab, a chimeric monoclonal antibody against the CD20 antigen. However, some patients are not fit enough to tolerate CHOP or they relapse after previous therapy with CHOP. Gemcitabine as a monotherapy is active and relatively non-toxic in the treatment of NHL. We investigated the toxicity and efficacy of a combination of gemcitabine with rituximab in a small series of elderly patients with high-grade B-cell lymphoma who had either a relapse after CHOP, or were medically unfit to tolerate CHOP as a first-line therapy. Gemcitabine was given at 1000 mg/m2/week x 3, q28 days; rituximab at 325 mg/m2/week x 4 in the first cycle, and on day 1 of all subsequent cycles. Seven patients have been treated. The median number of cycles given was 4. The major toxicity was haematologic: grade 3/4 leukocytopenia occurred in 4 patients, grade 3/4 thrombocytopenia in 3 patients. There were no episodes of clinically significant bleeding. One patient developed febrile neutropenia and died in the course of treatment; another patient developed non-Q-wave myocardial infarction possibly related to hydration pre-treatment to rituximab and erythrocyte transfusion. He recovered well after symptomatic therapy. In 7 patients, 2 complete and 3 partial remissions were achieved, with an estimated median time to progression of 12 months. This series of patients shows that the combination of gemcitabine and rituximab is feasible in this population not able to undergo standard poly-chemotherapy, shows promising activity, and merits further evaluation.