Effects of cholera toxin B subunits supplemented with 0.1% cholera toxin (CTB*) on systemic IgE antibody responses to ovalbumin (OVA) were examined in BDFI (H-2b/d), Balb/c (H-2d) and C3H (H-2k) mice given OVA intragastrically or intranasally. Two successive doses of OVA intragastrically administered to Balb/c and C3H mice induced little IgE response and resulted in almost complete unresponsiveness to subsequent intraperitoneal challenge with OVA in Al(OH)3, while the intragastric administration to BDF1 mice induced high IgE response and resulted in abrogation of the unresponsiveness to the subsequent challenge. The intranasal administration of OVA induced little IgE response and suppressed response to the subsequent challenge in any strain of mice. On the other hand, two successive doses of intragastric or intranasal OVA together with CTB* enhanced IgE response in all three strains and the subsequent challenge with OVA in Al(OH)3 induced higher IgE responses. These results suggest that CTB* augments IgE response to OVA and abrogates the unresponsiveness when administered orally or intranasally into mice together with OVA, regardless of the H-2 haplotype of the mice.