Repeated blood-stage Plasmodium chabaudi chabaudi AS challenge infections in BALB/c and C57Bl/6 mice result in increased serum immunoglobulin (Ig) E levels and splenic cytokine production. The genetic background of the host influences both the cytokine response as well as the development of IgE antibodies. BALB/c mice showed high interleukin (IL)-4 secretion from splenocytes after in-vitro stimulation with malaria antigen after repeated P. chabaudi challenges and this was closely followed by higher levels of total IgE. Despite slightly elevated serum IgE levels, splenocytes from C57Bl/6 mice did not secrete any detectable IL-4 but produced interferon (IFN)-gamma in response to malaria antigen-stimulation in vitro. These data suggest that induction of IgE antibodies during murine malaria infection is genetically regulated.