Human leukocyte antigen (HLA) genes are characterized by high levels of polymorphism and linkage disequilibrium (LD), important characteristics to study the genetic background of human populations and their genetic structure. Here, we analyse the allele distribution and LD extent of HLA class I and II in São Miguel Island population (Azores archipelago, Portugal).The sample set was composed of 106 healthy blood donors living in São Miguel Island obtained from the anonymized Azorean DNA bank. HLA class I (-A, -B and -Cw) and class II (-DRB1, -DQB1, -DPA1 and -DPB1) genotyping was performed by PCR-SSP Olerup SSP (GenoVision Inc.), according to the manufacturer's instructions.Genetic diversity values, based on the 7 loci, ranged from 0.821 both for HLA-DPA1 and -DQB1 to 0.934 for HLA-B, with a mean value of 0.846. Analysis of 5 HLA-A-Cw-B-DRB1-DQB1 haplotypes revealed that A*01-Cw*07-B*08-DRB1*03-DQB1*02 is the most frequent in São Miguel (7.9%) followed by A*24-B*08-Cw*07-DRB1*03-DQB1*02 (3.8%). In addition, even though the reports of high LD for HLA markers in worldwide populations, São Miguel islanders do not have extensive LD (average D' = 0.285).In summary, the results demonstrate high variability of HLA in São Miguel Island population as well as absence of genetic structure and extensive LD. The data here presented suggest that in São Miguel islanders autoimmune diseases studies will necessarily encompass a more focused analysis of HLA extended haplotypes as well as the evaluation of other non-HLA candidate genes.