AbstractMice were immunized with hapten [NIP, (4‐hydroxy‐5‐iodo‐3‐nitrophenyl)acetyl or TNP (2,4,6‐trinitrophenyl)] conjugates of Ficoll or pneumococcal polysaccharide type 14 (S14), and they were bled on days 10 or 14. Anti‐hapten and anti‐polysaccharide antibodies were determined from the sera or from fractions (IgM + IgA), IgG1, IgG2a, IgG3or IgG2hseparated by a gradual acid elution from protein A. Approximately one‐half of both anti‐hapten and anti‐polysaccharide antibodies was found in the IgM + IgA fraction. The subclass distribution of the IgG antibodies was dependent on the antigenic determinants. Polysaccharide antibodies were mostly in the IgG3fraction (36–62%) and in the IgG1fraction (18–36%). Hapten IgG antibodies were mostly in the IgG1fraction (38–74%); each of the other three subclasses contributed the average of 13%. These results provide the first evidence that antibodies to different determinants of one antigen have grossly diff