Gemcitabine is a pyrimidine analog that is active in patients with aggressive lymphomas and Hodgkin disease. This study assessed tumor response in patients with previously treated follicular or small lymphocytic non-Hodgkin lymphoma. This was a 2-stage phase II trial with the first stage requiring 2 of 13 responses to proceed to the second stage. Gemcitabine was given as a single agent to patients with previously treated follicular or small lymphocytic lymphomas. Gemcitabine was administered at 1250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Thirteen patients were treated with 1 to 6 cycles of chemotherapy. Two patients experienced grade 4 toxicity with neutropenia. No grade 4 nonhematologic toxicity was seen. There was 1 partial response and 8 patients (61%) had either minimal response or stable disease. Single-agent gemcitabine administered at this dose and schedule produced 1 partial remission and half the patients had stable disease. However, the study had to be stopped early because of lack of meaningful response.