It is well known that Behçet's disease (BD) is strongly associated with human leukocyte antigen (HLA) B51 in many ethnic groups. However, there has been no published report as yet with respect to this association among the Iranian people. Furthermore, since it is now known that the B51 antigen can be encoded by 21 alleles, B5101-B5121, we performed HLA-B51 allele typing as well as HLA class I genotyping of 48 Iranian patients with this disease. As a result, the frequency of the B51 allele was significantly higher (62.1%) in the patient group as compared with the ethnically matched control group (31.8%) (Pc=0.067, R.R.=3.51). In the genotyping of B51 alleles, 33 out of the 36 B51-positive patients possessed B5101 and the remaining 3 carried B5108. This study revealed that Iranian patients with BD also had a strong association with HLA-B51. In addition, this significantly high incidence of HLA-B51 was found to be caused by an increase in both the HLA-B5101 and HLA-B5108 alleles. However, there was no significant difference in the HLA-B51 allelic distribution between the patient and control groups.