Although an immune response to bacillus Calmette Guėrin (BCG) has often been associated with antitumor activity, the action mechanism(s) of intravesical BCG therapy for prophylaxis and treatment of superficial bladder cancer is not clearly understood. In an attempt to evaluate the roles of tumor necrosis factor (TNF)-α and lymphotoxin (LT) in the antitumor activity, TNF-α productivities by peripheral blood monocytes, serum levels of TNF-α, and LT productivities by peripheral blood lymphocytes were studied in superficial bladder cancer patients after six intravesical administrations of BCG. TNF-α productivities by peritoneal macrophages of guinea pigs were also studied after six intravesical administrations of BCG. The maximum TNF-α productivities by peripheral blood monocytes of superficial bladder cancer patients were seen after the fourth week of administration of BCG, and the serum TNF-α levels were also slightly increased after intravesical BCG administration in the superficial bladder cancer patients. LT productivities by peripheral blood lymphocytes of superficial bladder cancer patients were significantly enhanced and the maximum LT productivity was also seen after the third or fifth BCG administration. TNF-α productivities by peritoneal macrophages of guinea pigs were significantly enhanced and the maximum TNF-α productivity was seen after the second or third BCG administration. Our data might suggest that six consecutive intravesical BCG administrations could induce the increased productions of TNF-α and LT, which might play an important role in the antitumor activity in superficial bladder cancer.Although an immune response to bacillus Calmette Guėrin (BCG) has often been associated with antitumor activity, the action mechanism(s) of intravesical BCG therapy for prophylaxis and treatment of superficial bladder cancer is not clearly understood. In an attempt to evaluate the roles of tumor necrosis factor (TNF)-α and lymphotoxin (LT) in the antitumor activity, TNF-α productivities by peripheral blood monocytes, serum levels of TNF-α, and LT productivities by peripheral blood lymphocytes were studied in superficial bladder cancer patients after six intravesical administrations of BCG. TNF-α productivities by peritoneal macrophages of guinea pigs were also studied after six intravesical administrations of BCG. The maximum TNF-α productivities by peripheral blood monocytes of superficial bladder cancer patients were seen after the fourth week of administration of BCG, and the serum TNF-α levels were also slightly increased after intravesical BCG administration in the superficial bladder cancer patients. LT productivities by peripheral blood lymphocytes of superficial bladder cancer patients were significantly enhanced and the maximum LT productivity was also seen after the third or fifth BCG administration. TNF-α productivities by peritoneal macrophages of guinea pigs were significantly enhanced and the maximum TNF-α productivity was seen after the second or third BCG administration. Our data might suggest that six consecutive intravesical BCG administrations could induce the increased productions of TNF-α and LT, which might play an important role in the antitumor activity in superficial bladder cancer.