We report a novel phospholipase A(2) (PLA(2)), group XII (GXII) PLA(2), distinct from other cysteine-rich groups with a catalytic histidine motif, by its 20-kDa size and distribution of the 14 cysteine residues within the protein. Alternative spliced forms with distinct subcellular localization, designated GXII-1 and GXII-2, were identified by reverse transcription-polymerase chain reaction. Importantly, GXII PLA(2)s, in particular GXII-2 PLA(2), and group V PLA(2), but not group X PLA(2), were selectively expressed in murine type 2 helper T (Th2) clones and in vitro differentiated mouse CD4 Th2 cells as compared with type 1 helper T clones and cells. Stimulation with anti-CD3 appreciably up-regulated expression of GXII PLA(2)s and group V PLA(2) by steady state analysis of the Th2 cells as compared with type 1 helper T cells. These results suggest that group XII and group V PLA(2)s might participate in helper T cell immune response through release of immediate second signals and generation of downstream eicosanoids.