Rituximab is a chimeric monoclonal antibody that binds specifically to the CD20 antigen expressed in most B cell lymphomas. As single agent or in combination with chemotherapy rituximab has shown significant activity in patients with relapsing or refractory aggressive lymphomas. Because T cell rich B cell lymphomas (TCRBCL) also express the CD20 antigen, we decided to evaluate the efficacy and tolerability of the anti-CD20 monoclonal antibody rituximab combined with chemotherapy in four patients with either primary refractory or early relapsed TCRBCL. The chemotherapy regiment consisted of vinorelbin and gemcitabine, a combination with known efficacy in patients with refractory aggressive lymphomas. The patients received 6 cycles of rituximab at the dose of 375 mg/m(2), combined with vinorelbine 25 mg/m(2) and gemcitabine 800 mg/m(2) at 3-week intervals. Three complete responses and one partial response were observed among our four patients with refractory or early relapsed TCRBCL without significant adverse effects, indicating considerable efficacy of this combination. Therefore, rituximab should be tested in combination with chemotherapy in the front line treatment of patients with TCRBCL.