The overall objective of this project is the application of basic immunochemical techniques to the problems of clinical medicine. The specific aims of the project include: further characterization of the pharmacokinetic effects, metabolism and clinical efficacy of the Fab fragments of digoxin-specific antibodies; the use of a newly developed radioimmunoassay for dihydrodigoxin, an inactive digoxin metabolite, in studies of the metabolic conversion of digoxin to dihydrodigoxin in man; the experimental characterization of the basis for a clinically important interaction between quinidine and digoxin in man; the application of a newly developed propranolol radioimmunoassay to the study of serum concentrations of this beta-adrenergic drug in patients with cardiovascular disease; the continued development of new radioimmunoassay methods for the measurement of serum concentrations of other important molecules in health and various disease states; the use of antibodies specific for fragments of human fibrinogen in characterizing the action of proteolytic enzymes on fibrinogen in various immunological disorders of man; the development of a quantitative immunochemical method for determining the extent of monocyte contamination in supposedly pure human lymphocyte preparations; and, a more precise characterization of the human cells and cell products involved in the modulation of immunological responsiveness in health and in disease states.