The ability of ampicillin polymers to elicit passive cutaneous anaphylaxis (PCA) reactions in guinea pigs was analyzed. Mediating antibodies were raised in rabbits against a crude preparation of 6-aminopenicillanic acid (6-APA). It was found that large ampicillin polymers were potent elicitors, 1,000-fold better than benzylpenicillin polymers. Small polymers in high concentrations did not elicit PCA reactions but inhibited the activity of the larger polymers. This inhibition was more pronounced than that of ampicillin monomer. High molecular weight of ampicillin polymer in the amount of 0.1% in an ampicillin solution manifested its PCA activity. The tendency of ampicillin to polymerize, particularly when kept in solution, makes this observation worth considering. The PCA reactions described were penicilloyl-specific as verified by immunosorbent experiments.