We have isolated a novel gene that encodes a protein sharing significant similarity with myeloid antigen CD33. The complete cDNA contains an open reading frame of 1,326 nucleotides encoding 442 amino acids. The deduced amino acid sequence indicates that this molecule belongs to the immunoglobulin (Ig) superfamily and is likely to be a new member of the sialoadhesin sub-family. It is composed of three Ig-like domains; its high degree of similarity to CD33 (70% identity) in the first and second of these domains implies that the placenta-specific gene product is likely to be associated with cell-cell interaction. Northern-blot analysis revealed transcripts of four distinct sizes, 7.5 kb, 5.0 kb, 4.1 kb, and 2.0 kb, specifically in the placenta. Consequently, we termed this gene CD33L (CD33 antigen-like). An alternatively-spliced transcript encoding a 342-amino-acid peptide which lacked the transmembrane region and the cytoplasmic tail was also isolated. We mapped CD33L by fluorescence in situ hybridization (FISH) to human chromosome 19q13.3, where the CD33 gene is also located.