Prostaglandin (PG)D₂, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP). Involvement of DP in the formation of allergic asthma was recently demonstrated with DP-deficient mice. However, proinflammatory functions of PGD₂ cannot be explained by DP alone. We show here that a seven-transmembrane receptor, CRTH2, which is preferentially expressed in T helper type 2 (Th2) cells, eosinophils, and basophils in humans, serves as the novel receptor for PGD₂. In response to PGD₂, CRTH2 induces intracellular Ca²+ mobilization and chemotaxis in Th2 cells in a Gαi-dependent manner. In addition, CRTH2, but not DP, mediates PGD₂-dependent cell migration of blood eosinophils and basophils. Thus, PGD₂ is likely involved in multiple aspects of allergic inflammation through its dual receptor systems, DP and CRTH2.