The purpose of the proposed study is to define the genetic and biochemical basis of a naturally occurring disease in the dog, which is characterized by recurrent pyogenic infections resulting from defective intraneutrophilic microbicidal capacity. A series of studies are proposed which are designed to provide a basis of comparison between this and other related human and animal diseases. The proposed studies are modeled after those which have been used to delineate the structural, metabolic, and functional abnormalities in human neturophil dysfunction syndromes. Initial studies suggest that this disease which we have referred to as canine granulocytopathy syndrome (CGS) is similar to, but not homologous with any other documented human or animal host defense failure syndrome. The unique nature of this spontaneously occurring disease could made it a very valuable research resource. The use of the CGS as a model of neutrophil dysfunction syndromes provides previously unavailable opportunities for assessing the relative role of factors involved in the microbicidal event. The principle objectives of this research are to 1) establish a colony of affected animals and determine the mode of inheritance by controlled breeding experiments, 2) characterize the pathophysiology of the disease, 3) determine the functionality of affected phagocytic cells and other host mechanisms, and 4) define the mechanism of biologic dysfunction on a molecular basis. These investigations will contribute to the understanding of the processes and mechanisms involved in the postphagocytic handling of pathogens by neutrophils and could therefore make a valuable contribution to basic biomedical research.