The feasibility and efficacy of flexible, response-adjusted rituximab maintenance therapy in B-cell chronic lymphocytic leukemia (B-CLL) was investigated in 12 patients with an at least minor response to four weekly cycles of 375 mg/m(2) of rituximab induction therapy. Rituximab maintenance therapy consisted of infusions of 100 mg rituximab every 4 weeks. If disease progression occurred, either the rituximab dose was increased or the time between infusions was shortened. Treatment-related side effects led to discontinuation of rituximab maintenance therapy in three cases. Maintenance therapy was successfully conducted for > or =6 months in seven cases; three of these individuals have been on maintenance therapy for >1 year to 3.5 years so far. Long-term toxicity, as determined based on hematological and immunological parameters, was mild.