BACKGROUND Serologic measurements with recombinant birch pollen allergens, rBet v 1 and rBet v 2 (birch profilin), have shown that more than 95% of patients allergic to tree pollen mount high levels of IgE against rBet v 1, whereas only approximately 10% of the patients display rather low levels of IgE against rBet v 2. OBJECTIVE In this study an attempt was made to determine whether the different allergenicity of the major birch pollen allergen, rBet v 1, and a minor birch pollen allergen, rBet v 2, might be related to a different immunogenicity of the proteins as evaluated in experimental animal systems (mice and rhesus monkeys). METHODS Purified recombinant allergens were injected into mice and rhesus monkeys with aluminum hydroxide as adjuvant for elicitation of specific IgE responses. Antibody responses to the allergens were detected by immunoblotting, and time courses of immune responses were measured by ELISA. RESULTS In both animal models more than the 10-fold dose of rBet v 2 was required to induce IgE antibodies, and even then, the amount of specific IgE antibodies elicited with rBet v 1 was substantially higher than that induced by rBet v 2. It was noted that rBet v 2 formed stable polymers through disulfide bonds. CONCLUSIONS In two different animal models (mice and rhesus monkeys) the major birch pollen allergen, rBet v 1, induced substantially higher levels of IgE than rBet v 2. A reduced allergenicity of Bet v 2 caused by polymer formation would be in agreement with previous studies indicating reduced allergenicity of proteins on chemical polymerization.