The role of IgG antibodies in inducing or modifying allergic reaction has not been sufficiently clarified. The objective of this investigation is to elucidate the relationship between IgG antibodies and penicillin allergy, between IgG and IgE antibodies in allergic patients. Enzyme-linked immunosorbent assay and Radioallergosorbent test were used to examine eight kinds of specific IgG and IgE antibodies, including major antigenic determinants: benzylpenicilloyl (BPO), ampicilloyl (APO), amoxicilloyl (AXO) and phenoxomethylpenicilloyl (PVO), and minor antigenic determinants: benzylpenicillanyl (BPA), ampicillanyl (APA), amoxicillanyl (AXA) and phenoxomethylpenicillany (PVA), in the sera of 249 patients with penicillin allergy. Except BPA-IgG, seven kinds of antigenic determinants IgG antibodies levels were significantly higher than that of control group (P < 0.05). Positive rates of specific IgG and IgE were 47.0 and 57.8%, while positive rate of IgE and IgG together was 77.9%. The positive rate of IgG antibodies to major antigenic determinants (42.2%) was significantly higher than that of minor antigenic determinants (8.8%) (P < 0.05). The positive rate of IgG antibodies of patients with typical clinical symptoms after penicillin administration when skin tests were negative was significantly higher than that of patients with positive skin test (P < 0.01). There were no differences between the IgG positive rates to three kinds of determinants and that of all of eight kinds. The study indicates that IgG may be important in penicillin allergy with negative skin test and IgG antibodies to major antigenic determinants probably play a more important role in the process of allergic reaction.