The sequences of two immunoglobulin gamma 1 heavy chains involved in the formation of non-amyloid tissue deposits were determined in two patients (RIC and THR) affected with plasma cell monoclonal proliferation and heavy-chain-deposition disease. The proliferating plasma cells of patients RIC and THR synthesized truncated gamma 1 chains of 45 kDa and 24 kDa, respectively, carrying internal deletions of the first constant (CH1) domain (RIC) or of the CH1, hinge and CH2 domains(THR). The shortened gamma chains were associated with lambda light chains in the monoclonal IgG component present in the serum from both patients but not in tissue deposits which lacked any detectable light chains. Bone marrow plasma cells from RIC contained short gamma 1 heavy-chain transcripts in which a VDJ exon related to the VH2 subgroup was directly joined to the hinge exon; plasma cells from THR contained short gamma 1 transcripts with a VDJ exon related to the VH3 subgroup joined to the CH3 exon. In both cases, the truncated transcripts carried precise deletions of complete exons and used regular splice sites at the variable/constant junction, consistent with the hypothesis that they originated from abnormal splicing of primary transcripts from the productively rearranged heavy-chain genes. Striking abnormalities of the variable regions were found, especially in framework regions, including replacement of an invariant tryptophan residue in protein from THR, hydrophobic residues most likely exposed to the solvent and inversion of charged amino acids probably exposed on the surface of the molecule.