A number of orphan G-protein coupled receptors (GPR) have been reported as putative chemokine receptors. One previously reported orphan receptor is an incomplete PCR clone, called GPR2. Here we report the cloning of full-length human (h)GPR2 and mouse (m)GPR2 cDNAs, and the identification of GPR2 as a receptor for a novel CC chemokine called ESkine. hGPR2 is expressed at high levels in testis and small intestine, and at lower levels in other tissues. mGPR2 was expressed at high levels in small intestine, colon, lymph nodes, and Peyer's patches and at lower levels in thymus and spleen. Stimulation of L1.2/hGPR2 transfectants with hESkine induced their migration and resulted in intracellular calcium mobilization. These results provide evidence that GPR2 is a specific receptor for ESkine. We propose that GPR2 be renamed as CCR10. The expression pattern of mGPR2/CCR10 suggests that it may play a role in the homing/trafficking of leukocytes within intestinal and lymphoid environments.