Asthma is a complex and multifactorial disorder. Several studies have reported association between different HLA- DQB1 and HLA- DRB1 alleles and allergic asthma. The aim of the present study was to investigate the association of HLA-class II alleles and haplotypes, with total serum IgE and the results of the skin prick test in Iranian children with allergic asthma. A total of 112 patients with allergic asthma symptoms (75 males and 37 females) were selected randomly from the pediatric hospital. In some patients total serum IgE and prick test were determined. Data of this study shows that HLA-DRB1*12 significantly increased in asthmatic patients (4.5% vs. 0%, P-value=0.04). HLA-DQB1*0603 and 0604 alleles were significantly higher in asthmatics than those in normal controls (10% vs. 0%, P-value= 0.0001; and 9.3% vs. 3.7%, P-value= 0.04, respectively). The statistical significance was relinquished after p value correction for all alleles except for HLA-DQB1*0602 (Pc=0.03) and HLA-DQB1*0603 (Pc=0.0015). Conversely, HLA-DQB1*0501 and 0602 were decreased in asthmatics compared to normal controls (7.5% vs. 13.5%, P-value= 0.05; and 4% vs. 12.5%, P-value= 0.002, respectively). The mean of total IgE in patients was 483 IU, and it was significantly high about 1140 IU in asthmatic patients with positive skin prick test to house dust. The most frequent alleles in asthmatic patients with the total IgE>200 IU/mL were HLA-DRB1*11and 1401, HLA-DQA1*0505, HLA-DQB1*0301 and in patients with total IgE<200 IU/mL were HLA-DRB1*0301, 07 and 1301, HLADQA1*0201 and 0301, HLA-DQB1*0201. These data suggests that HLA-DRB1, DQA1 & DQB1 alleles and haplotypes might be implicated in susceptibility to allergy and asthma and serum IgE production. As asthma and atopy are multifactorial disorders, probably HLA genes are involved in the regulation of immune specific responses to common allergen.