While conducting a gene discovery effort targeted to transcripts of the prevalent and intermediate frequency classes in placenta throughout gestation, we identified a novel member of the TGF-beta superfamily that is expressed at high levels in human placenta. Hence, we named this factor 'Placental Transforming Growth Factor Beta' (PTGFB). The full-length sequence of the 1.2-kb PTGFB mRNA has the potential of encoding a putative pre-pro-PTGFB protein of 295 amino acids and a putative mature PTGFB protein of 112 amino acids. Multiple sequence alignments of PTGFB and representative members of all TGF-beta subfamilies evidenced a number of conserved residues, including the seven cysteines that are almost invariant in all members of the TGF-beta superfamily. The single-copy PTGFB gene was shown to be composed of only two exons of 309 bp and 891 bp, separated by a 2.9-kb intron. The gene was localized to chromosome 19p12-13.1 by fluorescence in-situ hybridization. Northern analyses revealed a complex tissue-specific pattern of expression and a second transcript of 1.9 kb that is predominant in adult skeletal muscle. Most importantly, the 1.2-kb PTGFB transcript was shown to be expressed in placenta at much higher levels than in any other human fetal or adult tissue surveyed.