Two new human genes encoding putative G protein-coupled receptors were cloned from genomic DNA following a degenerate PCR strategy. The predicted amino acid sequences of the proteins encoded by these genes have the characteristic motifs of chemokine receptors. This prompted us to name these genes CKR-L1 and CKR-L3. Nevertheless, the identification of their ligands has not been possible using 16 human chemokines in three different assays. The RNA expression pattern of CKR-L1 and CKR-L3 is also similar to that generally found for chemokine receptors. To a different extent, these genes are expressed in spleen, lymph nodes, and CD4+, CD8+ and CD19+ lymphocytes. CKR-L1 expression was also detected in monocyte/macrophages. The homology to chemokine receptors suggests that CKR-L1 belongs to the family of beta chemokine receptors, while CKR-L3 is more similar to alpha chemokine receptors.