Abstract The P2Y receptors (P2YRs) are a family of G protein-coupled purinergic receptors that are stimulated by ATP, ADP, UTP, UDP, and UDP-G, and their interaction induces a wide range of biological effects in various cells through phospholipase C activation, inositol triphosphate generation, and Ca2+ release from intracellular stores. In our previous study, we demonstrated that in neutrophils, ATP regulates chemotaxis and phagocytosis via P2YR. In the present study, we examined the distribution and function of P2YR in another innate immune cell type, basophils, the degranulation of which is associated with type I allergy. To date, P2YR have been subdivided into 8 different subclasses: P2Y1, 2, 4, 6, 11, 12, 13, and 14. Of these 8 subclasses, our RT-PCR results showed the predominant expression of P2Y2, P2Y4, and particularly P2Y6, which are known as uracil nucleotide-sensitive P2YRs. Interestingly, HPLC analysis indicated that basophils spontaneously secrete UTP, the ligand for P2Y2 and 4, whereas UDP, the ligand for P2Y6, is probably generated from UTP in a metabolic pathway. Although the addition of UTP and UDP did not directly induce basophil degranulation, these nucleotides clearly enhanced the degranulation induced by anti-IgE cross-linking. These results suggest that uracil nucleotides act as potent inducers of histamine release in basophils.