The suppressive effect of cleavable penicilloylated dextran (BPO-DEX), whose directly bound penicilloyl groups undergo hydrolytic cleavage within 3 days under physiological conditions, on murine IgE antibody formation against the benzylpenicilloyl (BPO) determinant was investigated in BALB/c and C3H mice. Intraperitoneal administration of BPO-DEX during either primary or secondary IgE responses to BPO ascaris produced a reversible suppression of BPO-specific IgE, while not affecting carrier-specific IgE antibody formation. Suppression of longer duration, at least 10 weeks, was achieved, however, by repeated administrations of BPO-DEX. BPO-DEX itself did not generate detectable BPO-specific IgE antibodies. These results suggest that BPO-DEX might be one of the promising tolerogens in the prevention of penicillin allergy.