Th1 and Th2 cells can be phenotypically distinguished by very few cell surface markers. To identify cell surface molecule that are specifically expressed on Th1 cells, we have generated a panel of mAbs that specifically bind the surfaces of in, urine Th1 but not Th2 cells. One of these Abs identified the NK cell receptor CD94 as a molecule also specifically expressed on the surface of Th1 cells. As in NK cells, CD94 is expressed on Th1 cells together with members of the NKG2 family of including NKG2A, C, and E. Cross-linking these receptors on differentiated Th1 tells in vitro costimulates proliferation and cytokine production with a potency similar to that obtained b cross-linking CD28. We propose that CD94 KG heterodimers may costimulate effector functions of differentiated Th1 cells.