A search of a mouse expressed sequence tag database for novel messenger RNAs (mRNAs) in the PRL/GH family has identified three clones that are homologous to the rat PRL-like protein A (PLP-A), PRL-like protein B (PLP-B), and decidual/trophoblast PRL-related protein (d/tPRP). Full-length complementary DNA clones for each of these three mouse mRNAs have been sequenced. Mouse PLP-A is predicted to be synthesized as a precursor of 227 residues and secreted as a glycoprotein of 196 amino acids; the secreted protein shares 78% identity with rat PLP-A. The open reading frame for mouse PLP-B encodes a protein of 230 residues; the putative mature glycoprotein of 201 amino acids is 66% identical to rat PLP-B. The third mouse complementary DNA clone encodes a precursor protein of 240 residues and a secreted glycoprotein of 211 amino acids with 64% identity to rat d/tPRP. All three mouse mRNAs are expressed specifically in the placenta or decidua. The highest levels of the PLP-A mRNA are detected on day 12, at which time expression is localized to a subset of trophoblast giant cells, especially those cells that line maternal blood sinuses. PLP-B mRNA levels are high on day 10 in decidual cells and on day 12 in spongiotrophoblasts. The mRNA similar to rat d/tPRP is present at high levels even earlier in gestation (day 8) and is localized to the decidual layer. The identification of PRL-related mRNAs in common between the mouse and rat indicates that the encoded hormones are evolutionarily conserved and, therefore, likely to play important roles in reproductive physiology.