This study was performed to investigate whether the gender and sex hormones play a role in susceptibility of the small intestine of mice to peroral infection with Toxoplasma gondii tissue cysts. Female animals died significantly earlier than males, and early mortality of females was associated with greater numbers of tachyzoites and severe necrosis in their small intestines. Treatment of female mice with testosterone resulted in markedly reduced intestinal parasite numbers and pathology. Thus, the gender and sex hormones are important factors for determining susceptibility of the small intestine to T. gondii infection.