HLA class II antigens are transmembrane glycosylated heterodimers composed of an alpha and a beta chain. Several of these chains are highly polymorphic. The structural bases of the polymorphism are nucleotide acid substitutions which are situated in the first domain (exon II) of alpha and beta genes. Specific sequences of these domains can be obtained by amplification of genomic DNA using the polymerase chain reaction. Polymorphic sites are recognized by restriction endonuclease treatment and separation of the DNA fragments by polyacrylamide gel electrophoresis. The resulting fragments of different lengths are used to identify different alleles. We used the above technique for typing the HLA-DQA1 alleles in 41 Tunisian diabetic patients. The frequency of DQA1*0301 was greatly increased compared with the control group. This was in agreement with previously published data in Caucasian and Japanese insulin-dependent diabetes mellitus (IDDM) patients, while the significant increase in the frequency of the DQA1*0501 allele was comparable with that of Caucasian IDDM patients but contrasted with a decrease in this allele in Japanese IDDM patients. Our results provide confirmation of the contribution of the DQA1*0301 allele to disease susceptibility in a Tunisian population.