Either four or eight weekly rituximab infusions in relapsed or refractory low-grade or follicular B cell non-Hodgkin's lymphoma (NHL) are well tolerated and efficacious. This phase II trial investigated the safety and efficacy of six weekly rituximab doses in chemotherapeutically pre-treated relapsed or refractory low-grade NHL patients. Sixty-eight patients (median age 64 years) received six i.v. rituximab infusions 375 mg/m2weekly. All patients had received one or more prior therapies (median 2; range 1–18). Forty-two patients had progressive disease and were evaluated for toxicity and efficacy; 12 of these required re-treatment with six weekly rituximab infusions. Twenty-six patients received rituximab as remission consolidation therapy and were assessed for toxicity only. No patients discontinued because of adverse events. Most adverse events were National Cancer Institute grade 1 (2–9%) or 2 (3–5%) and usually occurred during the first infusion. No hematological abnormalities were observed. Overall response rate was 59% (median time to response 2 weeks) and 10 of 12 re-treated patients responded. Median time to progression for all patients was 14 months and for responders 21 months. More than half the 42 patients evaluated for efficacy and more than 70% of the 25 responding patients still survived longer than 3 years after treatment. The safety profile and efficacy achieved in this study compare favorably with those seen with four or eight weekly doses in pre-treated low-grade NHL.