Objective    To investigate the structural recognition of a cross-reacting determinant in patients with penicillins allergy. Methods    Radioallergosorbent test (RAST) was used to detect eight kinds of specific IgE to penicillins in 133 sera of penicillin allergic patients. RAST inhibition tests were employed to identify the fine structure features recognized by IgE antibodies. PBMC obtained from subjects were stimulated with different chemical structure of penicillins, and identify the proliferative responses of peripheral blood lymphocyte (PBL). Results    The rate of positive reactions for the specific IgE antibodies was 59.40%(79/133). The positive cases only to one drug were 35(26.36%), the cross-reactivity cases among different drugs were 44(33.08%). RAST inhibition studies showed that penicillins and side-chain structure of penicillins showed good inhibitory activity. 6-Aminopenicillanic acid (6-APA) was the weakest inhibitor. Results of another serum indicated that 6-APA was the strongest inhibitors, while molecules representing their side-chains and drugs were proved to be the next best inhibitors. The results of the proliferative responses of peripheral blood lymphocyte showed that 6-APA, molecules representing their side-chains and drugs all can stimulate the proliferations of lymphocytes, and the proliferations of lymphocytes stimulated by the molecule representing their side-chains were lower than that stimulated by penicillins-treated groups. Conclusion    Partial cross-reactivity existed among different kinds of penicillins.6-APA and the groups, making up part of the different side-chains on penicillins, are all accounted for the cross-reactivity.