Currently available murine staphylococcal enterotoxin B (SEB) shock models require pretreatment with various agents to increase mouse sensitivity to SEB. This study was performed to show that C3H/HeJ mice are highly susceptible to intranasal SEB inoculation, which caused toxic shock without using pretreatment agents. For this purpose, mice were injected intranasally with different doses of SEB and observed for up to 1 month. The median lethal dose of SEB was determined using the probit procedure. Tissue samples were taken at different time points for histopathological examination. The LD(50) was found at 1.6 microg/g (95% fiducial limit (f.l.) 0.7 to 2.2), the LD(80) at 2.7 microg/g (95% f.l. 1.9 to 4.0) and the LD(90) at 3.6 microg/g (95% f.l. 2.7 to 6.4). Histopathologic examination revealed pulmonary edema and bronchopneumonia. Mucosal-associated lymphoid tissue first became activated, followed by increasing lymphocyte apoptosis and depletion. In the liver there were intralobular and portal inflammatory foci with increasing lymphocyte apoptosis and degenerative necrosis. The splenic white pulp was characterized by early activation and subsequent depletion of lymphoid follicle germinal centers. The thymus initially was activated, followed by increasing apoptosis and migration of lymphoid cells from the cortex to the medulla. The pathological features detected in the mice were similar to those of rhesus monkeys treated with SEB aerosol challenge.