PGD(2) is a major product of arachidonic acid metabolism by mast cells and is released in the lungs following allergen challenge. Activation of the classic PGD(2) receptor (DP receptor) results in stimulation of adenylyl cyclase, resulting in inhibition of platelet aggregation and smooth muscle relaxation. A second PGD(2) receptor has recently been identified and designated as the DP(2) receptor, or chemoattractant receptor-homologous molecule expressed on Th2 cells. PGD(2) acts through the DP(2) receptor to induce eosinophil chemotaxis, actin polymerization, calcium mobilization, and adhesion molecule expression. The most potent DP(2) receptor agonist yet identified is 15R-methyl-PGD(2), which has the unnatural R configuration at C(15). 15-Deoxy-Delta(12,14)-PGJ(2) is also a potent DP(2) receptor agonist that activates eosinophils at concentrations much lower than those required for its anti-inflammatory effects. Because of its critical location in the lung and its potent effects on eosinophils, PGD(2) may be an important proinflammatory mediator in asthma.