PGI(2) plays a key role in limiting Th2-mediated airway inflammation. In studies to investigate the mechanism underlying such regulation, we found that the PGI(2) receptor, IP, is preferentially expressed by effector CD4(+) Th2 cells, when compared with Th1 cells. Adoptive transfer of DO11.10 Th2 cells pretreated with PGI(2) resulted in considerably attenuated pulmonary inflammation and airway hyperreactivity in BALB/c recipient mice in response to OVA inhalation. This suppression was independent of increased cAMP levels, because pretreatment of Th2 cells with dibutyryl cAMP before transfer had no effect on airway inflammation. Moreover, PGI(2) pretreatment of Th2 cells suppressed the ability of the cells to infiltrate the lungs but not the spleen. In vitro studies showed that PGI(2) did not affect IL-4 and IL-5 production or the level of IFN-gamma by the T cells. However, the prostanoid strongly inhibited CCL17-induced chemotaxis of CD4(+) Th2 but not Th1 cells. The IP was implicated in this process since migration of wild-type Th2 cells in response to CCL17 was markedly reduced following treatment with PGI(2), whereas IP-deficient Th2 cells were unaffected and migrated effectively. Collectively, these experiments suggest that PGI(2), which is generated by endothelial cells during lung inflammatory response, serves to limit the influx of Th2 cells to the airways. Our results identify PGI(2)-IP as an important pathway for inhibiting allergic pulmonary inflammation by controlling recruitment of CD4(+) Th2 cells into the inflammatory site.