The management of relapsed or refractory B-cell non-Hodgkin's lymphoma (B-NHL) remains challenging. We investigated the efficacy and safety of salvage chemoimmunotherapy (CHASER) in patients with relapsed or refractory B-NHL who had radiographically measurable disease and adequate major organ function. The CHASER treatment consisted of: rituximab 375 mg/m(2), day 1; cyclophosphamide 1200 mg/m(2), day 3; cytarabine 2 g/m(2), days 4 and 5; etoposide 100 mg/m(2), days 3-5; and dexamethasone 40 mg, days 3-5. The treatment was repeated every 3 weeks up to a total of four courses in the absence of disease progression. Thirty-two patients were enrolled and received a median of four courses of treatment (range 1-4 courses) per patient. Twenty patients (63%) were previously treated with rituximab-containing regimens. The median age was 54 years (range 28-67 years). The treatment was generally well tolerated, with major toxicities being grade 4 neutropenia (n = 32), thrombocytopenia requiring transfusion (n = 28), and grade 3 transaminase elevation (n = 2). Overall response rates in the entire group, and in patients with indolent (n = 17) and aggressive (n = 15) diseases were 84%, 100% and 67%, respectively. Responses were observed similarly in patients with (n = 20) and without (n = 12) previous rituximab exposure (85% and 83%, respectively). Stem cell harvest was successful in 19 of 22 patients. The median time to treatment failure for the entire group was 24.5 months. This promising result of high activity and favorable toxicity profile warrants further investigation in large-scale multicenter trials.