By subjecting pneumococcus filtrates to ultrafiltration followed by repeated fractional precipitation with alcohol, Wadsworth and Brown (1) have obtained good yields of type-specific and species-specific polysaccharides in a relatively high state of purification. This report deals with the local reactions and the type-specific antibody response of non-pneumonic human subjects to injections of specific polysaccharides of Types I, IV, V, VII, and XIV pneumococci prepared by this method. (4,5) and also by Alston, Galbraith, and Stewart (6). Similar skin reactions were also elicited with varying frequency, using polysaccharides prepared by the same and by other methods, in normal subjects and in hospital subjects without pneumonia or recent intracutaneous injections (7,8,9,10). In such subjects, positive reactions to the initial injections were not correlated with the presence of circulating antibodies (7, 8, 9, 10) but the development of antibodies for the homologous pneumococcus type was stimulated by a single or by multiple intracutaneous injections (8,9,11,12).Alston and Lowden (10), using Type I and Type II specific polysaccharides prepared by the methods of Heidelberger, Sia, and Kendall (13) and of Heidelberger and Avery (14), respectively, observed in normal sub-1 This study was aided, in part, by a grant given in honor of Francis Weld Peabody by the Ella Sachs Plotz Foundation. jects a secondary cutaneous reaction consisting of redness, edema, and tenderness occurring in 2 to 5 hours and lasting 8 to 48 hours. A similar reaction had also been described by Finland and Sutliff (4) in occasional patients recovering from pneumonia in whom the reactions, induced by similar polysaccharides, were typespecific and began as a typical but intense immediate wheal and erythema. Similar reactions, both with and without the characteristic immediate phase were also noted in non-pneumonic subjects tested with autolysates from virulent and from avirulent strains (7).Tillett and Francis (15) and later Ash (16) demonstrated precipitins for the somatic, species-specific, carbohydrate, the so-called C fraction of Tillett, Goebel, and Avery (17), in the febrile stage of pneumonia and of many other acute infections but not after recovery from these diseases. Francis and Abernethy (18) reported immediate and delayed reactions, similar to those described above, which they obtained with the C fraction during the height of pneumonia and other febrile illnesses but not during convalescence and not in cases having a fatal termination.Differences in antigenic activity of type-specific carbohydrate substances derived in different ways from the same type of pneumococcus have been observed by many workers (19 to 27 inc.). Wadsworth and Brown (19) found that all of their so-called cellular carbohydrates contain phosphorus and nitrogen, produce purpura in mice, and differ from the corresponding soluble specific substance prepared by the earlier methods of Heidelberger, Avery, and others in their reaction with immune serums and in the respon...