Pregnancy-specific beta 1-glycoprotein (PS beta G), a major product of the placenta with unknown function, consists of a set of glycoproteins synthesized by the syncytiotrophoblast. We report here the molecular cloning of 3 cDNA encoding different members of the PS beta G family. Two clones (C, D) correspond to a single transcript undergoing differential splicing. The third one (E) originates from a different gene. All three clones have identical (C, D) or similar (E) coding sequences except for the last residues at their carboxyl end. They contain 93 residue motifs related to the ancestral Ig-like domain which makes them new members of this gene superfamily. A striking sequence similarity (50 to 60%) is observed between PS beta G and carcinoembryonic antigen (CEA)-related proteins. The evolutionary relationship between CEA and PS beta G points to a possible common function in the control of cell invasion and/or metastasis.