A systematic study has been conducted of the priming effect in the immunization against cholera toxin (CT). We demonstrate that a priming phenomenon can be achieved by synthetic peptides of the CT B subunit, leading (after a subsequent booster with a subimmunizing dose of the intact toxin) to an efficient anti-CT neutralizing antibody response. This effect is obtained even upon a single administration of a peptide conjugate and even by peptides that as such are not able to induce CT cross-reactive antibodies whatsoever. This effect is specific and dose dependent. A macromolecular carrier as well as an adjuvant are essential for the induction of anti-toxin response. In this respect, a totally synthetic priming agent, CTP3-poly(DL-alanyl)--poly(L-lysine), was adequate for an effective priming response. The specificity of the antibodies formed after the booster was mainly towards the whole CT molecule and only a small fraction of them were specific towards the peptide used for priming. The ability of synthetic peptides to prime the immune system towards a secondary stimulus with whole organism or native protein might be of general practical value, especially in endemic areas where the population is probably constantly exposed to a low level of a particular infectious agent. This exposure, which has no influence on the unprimed immune system, could serve as a booster in the case of individuals primed with an appropriate peptide, leading to a secondary immune response.