To investigate the mechanism of function of the OK-432 as a immunopotentiator, morphological studies of the spleen was carried out. OK-432 was administered by intravenous injection in single (0.1 KE/100g of body weight) or sequential (0.01, 0.025, and 0.05KE/100g of body weight for successive 3 days) doses to sensitized with sheep red blood cell (SRBC) and nonsensitized mice. One, 3, 5, 7 and 10 days after OK-432 administration, histological examination was performed by H&E, methylgreen-pyronin(MGP), and reticulin stains. 1) In OK-432 administered group, especially in sequentially administered group, proliferation of periarteriolar lymphatic sheath with altered cellular composition from small lymphocytes to plasma cells were prominent. 2) In groups with single administration of OK-432, germinal center of the secondary lymphoid follicle was distinct in 1st day, but becomes indistinct in 3rd day, and reticular cells and tingible body macrophages(TBM) of the secondary follicle were replaced by small- and medium-sized lymphocytes, lymphoblasts and pyroninophilic cells. In the sequential doses of OK-432 administered group, germinal center composed of pyroninophilic cells was indistinct at 3rd day, but became distinct after 5 days. 3) In sequentially group, large numbers of histiocytes and plasma cells were in the marginal zone of the white pulp. 4) Splenic red pulp was not altered morphologically in experimental groups. These results showed that OK-432 affected not only the periarteriolar lymphatic sheath, but the germinal center o the secondary lymphoid follicle and marginal zone. It suggests that OK-432 may be related to humoral immunity as well as to cell-mediated immunity.