In the field, male rodents are more frequently infected with hantaviruses than females. This study examined whether patterns of immune responses against hantavirus differed between the sexes. Male and female Long Evans rats (Rattus norvegicus) were inoculated with Seoul virus, and antibody and cytokine responses, as well as virus shedding were assessed. Males were more likely to shed virus in saliva, to shed virus through multiple routes (saliva, urine, and feces), and to have viral RNA in the spleen than females. Anti-Seoul virus IgG responses were higher in males than females. In both sexes, splenic IFNgamma and IL-4 production increased following infection. After infection, males had higher Th1 immune responses (i.e., IgG2a, IFNgamma, and IL-2) than females; in contrast, Th2 immune responses (i.e., IgG1, IL-4, and IL-10) were similar between the sexes. These data suggest that immune responses to Seoul virus differ between the sexes.