We have examined the CDR3 sequence and adjacent regions of immunoglobulin genes from B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Twenty-nine sequences (15 sequences from 13 low-grade MALT lymphomas, marginal zone B-cell lymphomas; 7 sequences from 6 high-grade MALT lymphomas; 7 sequences from 7 diffuse large cell lymphomas) were obtained after cloning of the polymerase chain reaction-amplified segments. In the low-grade MALT, high-grade MALT and diffuse large cell lymphomas, the mean length of the CDR3 region was 47.6+/-10.31 (range 21 to 60), 38.71+/-10.37 (range 27 to 57) and 40.86+/-3.34 (range 39 to 48) nucleotides, respectively. The length of the CDR3 region was significantly greater in the low-grade MALT lymphoma group than in the other two groups. CDR3 sequences in lymphoma cell clones of 14 cases showed 60 to 81% homology with autoantibody-associated lymphocyte clones including rheumatoid factor. The incidences of these autoantibody-associated lymphocyte clones were higher in the high-grade MALT (4/6) and diffuse large lymphomas (5/7) than in the low-grade MALT lymphoma (5/13). Cases with more than 70% homology at the nucleotide level were found to have 71 to 82% homology with autoantibodies at the protein level in the low-grade MALT lymphomas (2/13), and 67% homology in the high-grade MALT lymphomas (2/7). These results indicate that MALT lymphomas may be derived from the malignant transformation of autoreactive B-cells.