Several group B scavenger receptor cysteine-rich (SRCR) proteins have been shown to function as modulators in the immune response. Recently, we reported the cloning of a new member of this family, human Spalpha (hSpalpha). Herein we report the cloning and characterization of the mouse homologue of hSpalpha. Like its human counterpart, mouse Spalpha (mSpalpha), is a secreted protein containing three SRCR domains. Most lymphoid tissues express RNA transcripts encoding mSpalpha. Characterization of a genomic clone encoding the mature mSpalpha protein showed that each of the SRCR domains of mSpalpha is encoded by a single exon. Comparison of the sequence of mSPalpha with those of other published proteins indicates that it is the same as the recently reported protein named AIM (apoptosis inhibitor expressed by macrophages). Cell-binding studies with a mSpalpha immunoglobulin (mSpalpha-Rgamma) fusion protein indicated that mSpalpha is capable of binding to spleen-derived CD19+ B cells and minimally to peritoneal cavity-derived CD19+ B cells but not to peripheral blood-derived B cells. Spleen-derived CD3+ T cells also bound mSpalpha-Rgamma; however, no binding was observed to either peripheral blood mononuclear cells or peritoneal cavity-derived CD3+ T cells. The mSpalpha-Rgamma fusion protein was also shown to bind to the mouse cell lines WEHI3 (monocytic) and EL-4 (thymoma, T cell). The cloning of cDNA and genomic clones encoding mSpalpha and the identification of cells expressing a putative mSpalpha receptor(s) should facilitate in vivo studies designed to investigate the function of Spalpha in the immune compartment.