Background: This is the first comprehensive report of HLA antigens in Omanis, and the first application of HLA sequence-specific primer (SSP) DNA typing in a Gulf population. The objective was to compare the findings with other Gulf populations and assess their implications for disease association. Patients and Methods: HLA typing was carried out on 321 healthy Omanis. One hundred and twenty-six of these were typed for Class II antigens by low-resolution SSP DNA typing. The results were compared with other HLA antigen frequencies recorded from Kuwait and Saudi Arabia. Results: The Omani population was characterized by a very high incidence of HLA-DR2 (66), with associated HLA-DQ1 (76) and a reduced incidence of DR4, DR7 and DR53. The incidence of DR2 is the highest recorded worldwide. HLA-A11, A32, B17, B35 and B40 were significantly higher than in Kuwait and Saudi Arabia, and A9, B21 (B50) significantly lower (P(c) 0.05). HLA-B27 is very low in the Omani population (0.3). The high incidence of HLA-DR2 in Oman and disparities in the frequency of other antigens would indicate that there has not been any significant migration from northern Arabia. Class II DNA typing revealed that DR16 was the predominant split of DR2 (63), with DR15 being 18 and both DR15 and 16 being found in 6, giving a total of 87 for ″DR2″-associated antigens (serology of the same individuals gave a DR2 incidence of 74). The major disparity between serology and DNA typing was in the definition of DR4 (serology 8, DNA 14) and DR51 (53 vs. 70). Conclusion: The frequency of many HLA antigens in Omanis differs significantly from frequencies found in the populations of Kuwait and Saudi Arabia, possibly reflecting different migration patterns. The high incidence of HLA-DR2 in Oman may have important implications for disease association.