Control of cell proliferation is a basic biological problem central to the understanding of development and growth. Hormone-responsive cells are a good model to study this regulatory phenomenon. Three working hypotheses have been proposed to explain estrogen (E) induction of cell proliferation: a) E acts directly, b) E acts through the induction of growth factors, and c) that E neutralize the action of a plasma-borne inhibitor. Evidence supporting hypothesis c) has been gathered in recent years; these data indicate that the inhibitor is blood-borne and cell-type specific. Progress in this area of research requires that the putative inhibitor be purified. This will provide the tools to test which hypothesis is correct, and a better understanding of the mechanisms that control cell proliferation in multicellular organisms. Goals of this proposal are: l) to obtain a highly purified preparation of the plasma-borne inhibitor, 2) to obtain specific monoclonal antibodies using this preparation; and 3) to gather amino acid sequence information to ascertain the molecular identify of the inhibitor.//