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A major problem in the development of a particulate hepatolienographic agent is the prevention of particle aggregation upon contact with blood. When iothalamate ethyl ester, a particulate suspension for potential use as an hepatolienographic agent, was mixed with human or animal plasmas, it resulted in moderate to severe flocculation. In a study conducted to define the binding of plasma proteins to the iothalamate ethyl ester particles, plasma was reversibly adsorbed to various particle preparations. Fractions obtained by incubation of the particle-plasma complexes in buffers of increased ionic strength and decreased pH were subjected to polyacrylamide disc gel electrophoresis. The fraction containing the specifically bound proteins produced three distinct bands corresponding to prealbumin, albumin, and fibrinogen. Since the particles flocculated only when mixed with plasma, it is postulated that the fibrinogen-particle interaction is a major factor leading to particle agglutination.