The objectives of this study are to isolate, to homogeneity, progesterone binding globulin (PBG) from the serum of pregnant guinea pigs, determine the nature of the amino acids involved in the binding of steroids, determine the site of synthesis and etiology of induction of PBG, and study its function during gestation. PBG will be isolated by affinity chromatography using desoxycorticosterone hemisuccinyl-bovine serum albumin-Sepharose as the affinity resin. The nature of the amino acids present at the steroid binding site will be determined by reacting PBG with group-specific chemical reagents and characterizing those modifications which result in an alternation of steroid-binding characteristics. Affinity labels will be synthesized to confirm the results of the chemical modification studies and will be used in studies aimed at determining the function of PBG. The etiology of induction will be determined by a careful study of the time course of changes in serum levels of PBG during gestation in normal and fetectomized animals. The latter should aid in detecting possible inducers of PBG which might be produced by the fetus. The site of synthesis will be determined by examining tissues for PBG content, detecting C14-amino acid incorporation into PBG using immunoelectrophoresis, and examining tissues at the electron microscope level using the unlabeled antibody enzyme (peroxidase anti-peroxidase or PAP) technique of immunocytochemistry. The function of PBG will be probed using affinity labels and antibodies. These studies should lead to an understanding of the molecular basis of steroid-protein interactions and of the processes regulating the production of specific proteins synthesized during pregnancy. A greater understanding of the function of serum steroid-binding proteins should also be realized.