This study was performed to evaluate the prophylactic effects of trimethoprim-sulfamethoxazole (TMP-SMZ) in mice experimentally infected with virulent RH strain and avirulent Beverley strain of T. gondii. The mice infected with 1 x 10(5) tachyzoites were used in the measurement of mean survival days, and the mice infected with 10 cysts were used in the titrations of specific antibodies and enumeration of brain cysts. Mean survival days of mice were significantly increased in mice treated with TMP-SMZ as compared with spiramycin-treated and untreated control group. Mean survival days and survival rates of mice were increased according to the increment of dosages, and TMP-SMZ protected 100% of mice after fifteen daily dose of 24 mg/mouse or more administered orally. Toxoplasma-specific serum IgG and IgM antibody titers were significantly lower in mice treated with TMP-SMZ than those of spiramycin-treated and untreated control group. Toxoplasma cysts were not found in mice treated with TMP-SMZ at a dose of 24 mg/mouse or more per day, but the group of spiramycin treatment and untreated controls were found in the brain from 20 days after infection. The present results revealed that TMP-SMZ can be used as a prophylactic agent against murine toxoplasmosis after intraperitoneally challenges with the virulent or avirulent strain of T. gondii.