Tumor-infiltrating lymphocytes consist predominantly of T cells, whereas B cells, plasma cells, and natural killer cells are observed with different degrees of frequency. We investigated the nature of tumor-infiltrating B lymphocytes (TIB) in human lung cancer. First, to examine the ability of immunogloblin production by TIB, cancer tissues were subcutaneously transplanted in severe combined immunodeficient mice, and the murine serum was examined for the concentration of human immunogloblin. Human IgG (huIgG) was detected in the serum of all 12 mice engrafted with lung cancer tissues. huIgM was almost undetectable. The levels of huIgG reached a peak approximately 6 weeks after engraftment and gradually decreased but were detectable until 20 weeks postengrafment. Serum from a large cell carcinoma-engrafted mouse reacted with a protein of 60 kDa derived from lung cancer cell lines (PC-9, Sq-1) and autologous tumor cells but did not react with cell lysates of normal lung tissue. Serum from an adenocarcinoma-engrafted mouse reacted with two proteins, 33 and 55 kDa, derived from lung cancer cell lines (PC-9, Sq-1, A549) and autologous tumor cells but did not react with the lysate of normal lung tissues. These results suggest that B cells infiltrating lung cancer tissues produce IgG that recognizes common tumor-specific antigen.