Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with promising therapeutic activity in the lymphoproliferative disorders and in particular in low-grade non-Hodgkin's lymphoma (LG-NHL). In order to evaluate FLU in combination with other antineoplastic agents, we used a three-drug combination of FLU, mitoxantrone and prednisone (FMP) to treat 18 patients with recurrent LG-NHL. The FMP regimen was as follows: FLU, 25 mg/m2 i.v. on days 1 to 3; mitoxantrone, 10 mg/m2 i.v. on day 1; prednisone 40 mg i.v. on days 1 to 5. Of the 18 patients, 4 (22%) achieved complete response (CR), 9 (50%) partial response, and the remaining 5 showed no benefit from the treatment. The 4 CR patients are still in remission after 4, 6, 6, and 8 months, respectively. The median duration of overall survival of all patients was 9 months. The major toxic effects observed were neutropenia (50%) and infections and/or febrile episodes (17%); no fatalities due to drug side effects occurred. These results confirm the efficacy of the fludarabine-mitoxantrone combination-containing regimen in inducting a good remission rate with moderate side effects in recurrent LG-NHL.