We have isolated cDNAs of the murine type II TGF-beta receptor and have found a conserved cytoplasmic domain, but a less extensive homology in the extracellular receptor domain between the human and murine homologues. In situ hybridization analysis of the mouse fetus during mid gestation localized the expression of this receptor to various developing tissues, primarily in the mesenchyme and epidermis. This expression pattern correlates well with the expression of TGF-beta in general and especially TGF-beta 1, suggesting that TGF-beta 1 exerts its developmental role through this receptor in an autocrine or paracrine fashion. Type II receptor expression was not detected in the central nervous system and developing cartilage. These tissues lack TGF-beta 1 expression but express TGF-beta 2 and/or TGF-beta 3, suggesting that they may exert their activities through separate receptor isoforms. In addition, the efficient binding of TGF-beta 1, but not TGF-beta 2, to the cloned type II receptor strengthens the likelihood that additional type II receptor isoforms exist which display preferential binding to TGF-beta 2 and have their own defined role in development.