The proposed studies continue a long interest in hemostatic mechanisms and related phenomena, now stressing the role of cells. Emphasis will be placed upon newly discovered inhibitory properties of peripheral blood mononuclear cells against the activation of Hageman factor (HF, factor XII). Current experiments are aimed at its purification and biologic role in maintaining the fluidity of blood; a similar property has been detected in supernates of endothelial cell cultures. To facilitate these studies, improved purification methods for HF and high molecular weight kininogen are under development. Hormonal regulation of the plasma titer of HF will be explored in the light of evidence that estrogens, prolactin and corticosteroids increase the titer. Since HF and prolactin synthesis may be determined by genes on chromosome 6, linkage between these genes will be sought. Studies of the acquired immunodeficiency syndrome in classic hemophilia will be continued, as well as examination of the inhibition of phytohemagglutinin-induced lymphocyte proliferation and interleukin-2 liberation by fractions of plasma in lyophilized antihemophilic factor (factor VIII) preparations. Other experiments will examine properties of an inhibitor of the generation of monocyte coagulant activity elaborated by endothelial cells; factors modulating tissue plasminogen activator produced by melanoma cells; the effects of fibrinogen degradation products upon human neutrophil function; and characterization of a monocyte-derived growth factor and its relationship to other growth factors. As always, vigorous attempts will be made to learn more about the physiology of hemostasis and thrombosis through the study of suitable patients.