Comparative structural studies of membrane-bound (mu m) and secretory mu chains (mu s) obtained from normal mouse spleen B lymphocytes and plasma cells were performed on CNBr digests of biosynthetically labelled chains. The purified major CNBr fragments were further digested with trypsin or Staphylococcus aureus V8 protease, and analyzed by high pressure liquid chromatography. The data show that mu m and mu s chains exhibit a very similar if not identical polypeptide structure over most of the four constant domains (from position N151 through N551), but that, in contrast, the mu m-C-terminal tail is different from mu s and contains a very hydrophobic segment. A combination of proteolysis, hydrophobic absorption and partial N-terminal sequencing of the hydrophobic fragment of mu m revealed in this region of the molecule a portion of sequence in perfect agreement with the structure predicted from the nucleotide sequence of the corresponding cDNA. The sequence of the C-terminal residues of mu m, which is different from that of mu s, could not be established, because of an apparent heterogeneity of mu m chains probably due to a great susceptibility to proteolysis of their C-terminal extremity.