Systemic immediate reactions including anaphylaxis to gelatin in vaccines have been reported. However, the number of such reports is very small compared with the number of children exposed to gelatin. The present study was designed to investigate whether susceptibility or resistance to gelatin allergy is associated with human leukocyte antigen (HLA) class II gene. Blood samples were obtained from 49 patients with gelatin allergy and specific IgE to gelatin. DNA-based HLA class II typing was performed to determine the DRB1, DQB1 and DPB1 alleles. Genotype frequencies were compared with those found in 240 unrelated controls. The frequency of DQB1*0303 (55.1%) was significantly higher in the patients than in the control subjects (32.1%). The frequency of DPB1*0402 was also significantly higher in the patients (32.7%) than in the control subjects (15.4%). On the other hand, the frequency of subjects carrying DRB1*15 (DRB1*1501 and DRB1*1502) was significantly lower among the patients group (18.4%) than among the controls (40.8%). We found that DQB1*0303 and DPB1*0402 were positively associated with the IgE response for gelatin, while DRB1*15 was negatively associated with it.