An antimicrobial polypeptide was isolated and purified from the acid soluble proteins of human LAK cells. Its N-terminal amino sequence was identical to HMGN2 (high mobility group nucleosomal binding domain 2). Mass spectrum identification and Western blotting analysis also indicated its individual character of HMGN2. The antimicrobial assay showed that MICs of the recombinant HMGN2 against E.coli ML-35p (an ampiciline-resistance strain), Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231 were 12.5, 25, and 100 mg/L respectively. In contrast, the recombinant holo-HMG-17 was inactive against Staphylococcus aureus ATCC 25923. The immunocytochemistry staining, ELISA, and Western blotting revealed that HMGN2 was present in the cytoplasm of mononuclear leukocytes and released to the extracellular environment when stimulated with IL-2. The results indicated that HMGN2 was a new effector molecule of human LAK cells.