T helper cell type 1 (Th1) and 2 (Th2) play central roles in immune regulation. To identify the novel genes differentially expressed between Th1 and Th2 cells, CD4+ T cells were isolated from DO11.10 transgenic mice and induced under Th1 or Th2 conditions. Microarray showed differential expression of neutrophilic granule proteins (NGP) between Th1 and Th2 cells. NGP was first identified as a myeloid-specific granule protein with homology to the cystatin superfamily. Here we confirmed greater expression of NGP in Th2 cells by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction analysis. We also showed that the expression of NGP mRNA had a peak expression after 5 d culture under Th2- but not Th1-biasing conditions. Antibody against NGP was prepared, and in concert with the results of mRNA analysis, the level of NGP protein in Th2 cells detected by Western blot analysis was also higher than that in Th1 cells. GFP-NGP fusion proteins overexpressed in HeLa cells were localized to the cytoplasm. These results suggest NGP is a novel marker distinguishing Th2 from Th1 cells and maybe a novel cytokine secreted by Th2 cells.