To investigate the effect of tumor removal and administration of OK432 on the splenic natural killer (NK) cell activity in the subcutaneous tumor bearing rats, NK cell activity assay using a 4-hour 51Cr release assay and flow cytometric analysis for NK cell population were performed. The results were as follows: 1. Splenic NK cell activity and population in the subcutaneous tumor bearing rats decreased along with the growth of the tumor. 2. The rats with subcutaneous tumor removal showed decrease of splenic NK cell activity, but splenic NK cell population was not decreased. 3. In the rats with subcutaneous tumor removal and OK432 administration, splenic NK cell activity was significantly increased 1 week after administration of OK432 and then gradually returned to normal, whereas increase of NK cell population was not significant. In the present study, splenic NK cell activity was significantly decreased despite removal of subcutaneous tumor. But with the administration of OK432, splenic NK cell activity returned to normal. Considering the role of NK cells on the first line of defense against the metastatic implantation of circulating tumor emboli, we suggest that perioperative administration of immunopotentiator such as OK432 may improve the patient's outcome after surgery of human neoplasm.