A 72-year-old patient with relapsed non-Hodgkin's lymphoma (diffuse large B-cell type) in the tongue was treated with irinotecan (CPT-11) as the 4th salvage therapy. A two-thirds reduced dose of 40 mg/m2 of CPT-11 was administered, as were granulocyte-colony stimulating factor and antidiarrheal agents. Complete remission was achieved. Although grade 3 leukopenia and grade 1 diarrhea were observed, these adverse reactions did not interrupt the treatment schedule and CPT-11 was administered without interruption for a total of 12 weeks. Despite the dose reduction, the area under the concentration-time curve of SN-38, the active metabolite of CPT-11, was nearly equal to the values reported in phase I and II studies of CPT-11. The patient's ratio of SN-38 to the SN-38 glucuronide (SN-38G) was low, suggesting a low risk of diarrhea. The optimal dose modification provided a sufficient amount of the active metabolite. Supportive therapy managed therapy-related toxicities and resulted in a stable treatment schedule. This is a rare case of a patient successfully treated with CPT-11 after a 4th relapse, in which the agent was administered at the total dose of 960 mg/m2, despite the patient's advanced age.