In this work, we wanted to clarify if differences in antibody (Ab) and particularly in secretory immunoglobulin A (IgA) responses following homologous or heterologous rotavirus infection could be explained by different priming of specific T helper (Th) cells. We compared the Ab responses from suckling BALB/c mice orally inoculated with either a heterologous simian (SA11) or bovine (RF) rotavirus or a homologous murine rotavirus (EHPw), as well as the profile of cytokines produced by spleen cells after in vitro restimulation. Oral inoculation of EHPw and SA11 induced a similar pattern of Ab with mucosal and serum IgA associated with serum IgG with equal levels of IgG1 and IgG2a, whereas RF elicited a weak humoral response. We found that these strains induced the same mixed Th1/Th2 pattern of cytokine production by spleen cells with IFN-gamma and IL-5 as well as IL-10, but not IL-2 or IL-4. These findings suggest that the induction of immune response is probably not different between these strains. Other factors such as the amount of antigen, strain immunogenicity, and other cytokines, particularly produced in effector sites, remain to be considered in order to better explain the differences in secretory IgA following homologous or heterologous rotavirus infection.