TGF-B occurs in a latent complex of high M,. We report the cDNA cloning and an initial structural and functional characterization of a component of the large latent TGF-pl complex, denoted TGF-PI binding protein (TGF-pl-BP). Most of the sequence of fibroblast TGFfil-BP is made up of cysteine-rich repeats of two different kinds; there are 16 EGF-like repeats and three repeats with a distant resemblance to EGF, but of a distinct type hitherto not found in any other protein. Phydroxylated asparagine residues were identified in two of the EGF-like repeats. TGF-p&BP purified from human platelets is considerably smaller than the fibroblast form (125160 kd vs. 170190 kd), suggesting that there is alternative splicing of the TGF-pl-BP gene or that TGF-pl-BP undergoes cell-specific proteolysis. TGF-Bl-BP was found not to bind and inactivate TGF-01; its role in the latent complex is discussed.