Pregnancy-specific glycoprotein (PSG) constitutes a major component of serum of pregnant women and appears to be essential for a successful pregnancy. Its function is, however, still unknown. Because of the evolutionary divergence between human and rodent PSG, functional studies may require a primate animal model. We have characterized PSG transcripts in a baboon placenta cDNA library and analyzed baboon genomic DNA. The main PSG isoform had the domain structure N-A1-B2-C similar to the human type IIa isoform. The type I isoform (N-A1-A2-B2-C) was also expressed. Fifteen similar PSG genes were identified of which at least nine were simultaneously expressed in third trimester baboon placenta. Thus, the baboon PSG family was as complex as that of humans. Recombinant baboon PSG (isoform IIa) had a molecular weight of 38 kDa and reacted with antibodies against human PSG. Comparative analysis of 43 N-domain amino acid sequences of PSG from four species and nine primate carcinoembryonic antigen subgroup N domain sequences identified a number of residues in the GFCC′C′′ β-sheet and FG loop that are probable candidates for PSG binding to its putative ligand.