Stings from bees and wasps can cause systemic allergic reactions in sensitized patients. However, the mystery of why some cases develop allergic reactions while others do not, remains poorly understood. We investigated whether particular human leukocyte antigen (HLA) class I and class II genes contribute to the development of venom allergy. A total of 21 bee and/or wasp venom sensitive patients who had life-threatening allergic symptoms after a sting, and positive diagnostic tests (Group 1), were included in the study. Thiry-seven healthy subjects without venom allergy (Group 2) were selected as the control group. HLA -class I (A-C) and class II (DR, DQ, DP ) typing was performed by PCR-based techniques. HLA -B*18 and HLA -Cw*07 alleles was found more frequently in Group1 than in Group 2 (14.3 percent vs 2.7 percent, p=0.026, and 31 percent vs 14.9 percent, p=0.036, respectively). Furthermore, HLA -A*01 allele frequency had a trend to be higher in Group 1 than in Group 2 (14.3 percent vs 4.1 percent, p=0.055). However, the frequencies of HLA -A*03 and HLA -Cw*03 alleles were increased in Group 2 compared to Group 1 (20.3 percent vs 7.1 percent, p=0.049 and 10.8 percent vs 0 percent, p=0.024, respectively). Among HLA -class II genotypes, HLA -DQB1*03 allele was significantly increased in Group 2 (60.9 percent vs 38.1 percent, p=0.018), while a higher frequency of HLA -DR B1*03 and HLA -DR B1*14 alleles showed a tendency statistically significant in Group 1 (9.5 percent vs 1.4 percent, p=0.057 and 11.9 percent vs 2.7 percent, p=0.058, respectively). HLA -B*18 and HLA -Cw*07 alleles may probably be associated with susceptibility to venom allergy, whereas HLA -A*03, HLA -Cw*03 and HLA -DQB1*03 seem to be protective markers in a small Turkish population.