Rituximab is a human-mouse chimeric monoclonal antibody that has demonstrated efficacy against non-Hodgkin's lymphoma (NHL). There is a powerful rationale for combining rituximab treatment with chemotherapeutic agents that have also shown efficacy in NHL, since the mechanisms of action are distinct and there is also evidence that rituximab may sensitize chemoresistant tumor cells to the actions of cytotoxic drugs. A study of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemoimmunotherapy has been carried out in 40 patients with low-grade NHL. In the 35 patients who completed the study, the overall response rate was 100%, with 63% achieving a complete response. Median time to progression has not yet been reached at 47.2+ months. Molecular analysis (polymerase chain reaction) showed that CHOP plus rituximab (unlike CHOP alone) could completely clear blood and bone marrow of cells containing the bcl-2 gene translocation, a molecular marker of NHL cells. Rituximab can therefore add to the efficacy of CHOP without significantly increasing toxicity. A further study is underway to determine whether similar efficacy with less overall toxicity can be achieved using rituximab in combination with fludarabine.