The aim of our phase II study was to determine the effectiveness of combined chemotherapy consisting of 2-hour intravenous infusion of 2-CdA, mitoxantrone and dexamethasone (CMD) regimen in the treatment of heavily previously treated patients with refractory or relapsed low grade non-Hodgkin's lymphoma (LGNHL). All of the 14 patients had clinical stage IV disease, most of them had B symptoms and elevated LDH levels. All cases were refractory to standard chemotherapy or had recurrent relapses having received at least 5 courses of prior chemotherapy. All patients received at least one cycle of CMD (range, 14). A total of 35 courses of CMD were given to the entire group. Complete response (CR) was obtained only in one patient (7.1%) and partial response (PR) in 3 (21.4%) with an overall response rate of 28.5%. The major toxicity was myelosuppression and 35% of the patients had infection. One patient died of sepsis. These results suggest that the addition of other drugs to 2-CdA in heavily treated patients with refractory or relapsing disease may not be more advantageous when composed to giving 2-CdA alone.