Gastric Helicobacter pylori (HP) positive extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) develops during chronic antigenic stimulation with specific T-cell help. Chemotherapy that acts both on the malignant B-cells and on T-cells in the microenvironment, i.e. nucleoside analogs, might therefore be an attractive treatment. In 14 patients with gastric MALT lymphoma treated with fludarabine, alterations in T-cell subsets were studied in subsequent peripheral blood samples and in gastric biopsies. Treatment with fludarabine resulted in a steep decrease in T-cell subsets in peripheral blood samples. By contrast no decrease in T-cell populations was observed in subsequent gastric biopsy samples and a moderate increase was observed in relative infiltration with CD3 +, CD4 + and CD8 + cells. In addition an increase in density of FOXP3 + cells (i.e. Tregs) was seen (p = 0.047). These alterations in different T-cell subsets were not observed in gastric biopsy samples of patients treated with HP-eradication only.