Two distinct genes are present in the human genome encoding receptors for human interleukin-8 (hCXCL8), referred to as hCXCR1 and hCXCR2. While it seems clear that orthologous genes are present in the genomes of several mammals, the existence of a gene encoding an ortholog of hCXCR1 in the mouse has thus far been controversial. We have isolated a cDNA that is highly similar to the cDNAs of hCXCR1 and hCXCR2, but is clearly distinct from the cDNA encoding mouse CXCR2 (mCXCR2). The encoded protein, designated mouse CXCR1-like (mCXCR1-like), shares 64, 57, 57, and 89% identical amino acids with hCXCR1, hCXCR2, mCXCR2, and rCXCR1-like, respectively. The gene encoding mCXCR1-like was mapped to mouse chromosome 1 and its genomic organization was determined to be very similar to the organization of the gene encoding hCXCR1. Like hCXCR1, mCXCR1-like was found to be expressed at the mRNA level in neutrophils. In addition, mRNA encoding mCXCR1-like was detected in liver, kidney, and spleen. In spleen, mCXCR1-like transcripts were predominantly found in CD4+ T cells. In liver, mCXCR1-like transcripts were identified in residual CD3+ T cells and macrophages, suggesting that mCXCR1-like may regulate inflammatory and immunological processes in the liver. When expressed as a recombinant protein, mCXCR1-like was not activated by a large panel of known CXC chemokines of human and murine origin. These findings suggest that a homolog or ortholog of hCXCR1 is expressed in the mouse to be activated by a hitherto unknown CXC chemokine of the mouse.