Behçet's disease is a multi-system inflammatory disorder of unknown etiology. The disease is more prevalent in Eastern Mediterranean countries and Japan where there is a linkage to HLA-B51. Mexican Mestizos are suitable subjects for studying the role of ethnicity in the susceptibility to Behçet's disease. High-resolution HLA class I and class II typing was performed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) reverse dot blot and PCR-single-strand polymorphism in 32 patients with Behçet's disease and 99 healthy ethnically-matched controls. A significant increased frequency of HLA-B(*)44 (P = 0.02; OR = 2.78; CI 95% = 1.1-7.7), HLA-B(*)52 (P = 0.02; OR = 5.33; CI 95% = 1.07-29.1), and HLA-B(*)56 (P = 0.003; OR = 4.19; CI 95% = 3.37-5.21) as well as HLA-DRB1(*)01 and HLA-DRB1(*)13 (p = 0.007; OR = 3.36; CI 95% = 1.22-9.27) was found in Mexican patients with Behçet's disease when compared to controls. The low frequency of native markers in Mexican Mestizo patients with Behçet's disease suggests that genetic admixture between Eastern Mediterraneans and Orientals with Amerindians is a recent event that increased the risk of developing Behçet's disease in the Mexican population.