Experimental studies were performed to clarify the mechanism of facilitation of tumor metastasis to the lung by operative stress, using an experimental model in which 5-week old female Sprague-Dawley (SD) rats were inoculated with a low antigenic and easily metastasizable tumor, MRMT-1. In particular, relevance of adrenocortical hormones to the facilitation of tumor metastasis was examined. Furthermore preventive effects of preoperative administration of a nonspecific immunopotentiator, OK-432, were examined. Number of metastatic nodules was increased significantly by operative stress and the increase was proportionate to severity of the stress. The facilitation of metastasis by operative stress was significantly inhibited by preoperative OK-432 administration. In adrenalectomized rats, no such facilitation of metastasis by operative stress was observed. After administration of 2.5 to 20mg of hydrocortisone, number of metastatic nodules increased dose-dependently. The increase in metastatic nodules by administration of 5mg of hydrocortisone was inhibited by preoperative OK-432 administration. Thus it was concluded that facilitation of tumor metastasis by operative stress was proportionate to severity of the stress, and one of its essential causative factors was the stress-induced adrenocortical hypersecretion, which suppressed immunity of the host. Administration of OK-432 was effective for counteracting the stress-induced facilitation of metastasis.