LTN and OK-432 combined therapy is effective for controlling Th1/Th2 balance. We tried a repetitive administration of LTN and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. Of all 11 lesions of the 10 cases, 7 revealed complete remission and 1 revealed partial response. The level of IL-12 (p70) and IFN-gamma in ascites of two gastric cancer patients after the second administration of LTN and OK-432 was much higher than those after the first administration, whereas the level of IL-10 was not suppressed strongly. In 8 lesions that we could confirm complete remission or partial response, 7 lesions were improved after two or three administrations of LTN and OK-432. In conclusion, a repetitive intracavital administration of LTN and OK-432 is effective for malignant effusion.