We describe a Xenopus P2Y receptor that shares only weak homology with members of the mammalian P2Y family, being most similar to human P2Y 11 . When activated by nucleotide analogs, it stimulates both calcium and cAMP mobilization pathways, a feature unique, among mammalian P2Y receptors, to P2Y 11 . Activity can be blocked by compounds known to act as antagonists of mammalian P2Y 11 . Genomic synteny between Xenopus and mammals suggests that the novel gene is a true ortholog of P2Y 11 . Xenopus P2Y 11 is transcribed during embryonic development, beginning at gastrulation, and is enriched in the developing nervous system.