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The clinical and pathological similarities between rheumatic fever in man and serum sickness in man and the rabbit have been observed by many (1)(2)(3)(4)(5)(6)(7)(8). But the value of serum disease of rabbits as an experimental tool has been limited by our ignorance of the pathogenesis of the cardiac and arterial lesions which accompany it. Some of the difficulty in understanding the factors responsible for these rheumatic-like (4, 9) lesions may be due to the multiple antigenic components in horse serum which may obscure cause and effect relationships. In recent experiments from this laboratory the lack of correlation between certain antemortem observations (Arthus reaction, humoral antibody levels, etc.) and the development of arterial and cardiac lesions was emphasized and it was suggested that more information might be gained by studying the effects of injecting large quantities of purified proteins (10).Meanwhile Hawn and Janeway (11) have investigated the effects of single large injections of highly purified bovine albumin and gamma globulin into rabbits. Their results indicate that the lesions resulting from the injection of purified beef gamma globulin tend to be localized to the renal glomeruli and to develop relatively quickly, while those following the injection of beef albumin are largely confined to the arteries and heart valves and are delayed. Further investigations of this type seem justified since an understanding of these selective local reactions might add much to our knowledge of tissue hypersensitivity and its relationship to rheumatic fever and g]omerulonephritis in man.The experiments which are reported here represent an extension of this type of study in which the antemortem and pathological responses of rabbits to several partially purified fractions of horse serum protein were observed. Inasmuch as previous reports of the lesions of rabbit serum disease have been largely descriptive, we propose to present our pathological data so that the comparative frequency and relative proportions of the lesions in the various organs and tissues are apparent.