We examined the immune response of Balb/c mice to antigens prepared by conjugating 2-phenyloxazolone (phOx) to a foreign protein, ovalbumin (OVA), or a self-protein, mouse serum albumin (MSA), in order to study how these chemical modifications would affect immune recognition. We found that anti-OVA antibodies and CD4(+) T cells produced by OVA immunization reacted with OVA as well as with phOx-OVA. Anti-phOx antibodies were produced by phOx-OVA immunization and, interestingly, T cells from these mice reacted only with phOx-OVA but not with the intact OVA. These results suggested that the classical model of hapten-carrier immunization, in which B cells specific to hapten are activated with assistance from T cells specific to a carrier protein, might not be a major route for production of anti-hapten antibodies in hapten-carrier immunization. Furthermore, phOx-MSA immunization induced production of anti-phOx antibodies, which could not be accounted for in terms of the assistance of carrier-specific T cells because of the absence of MSA-specific T cells. Therefore, we proposed a new model in which anti-hapten B cells are assisted by T cells specific to the haptenated carrier.