BACKGROUND: Alzheimer's disease (AD) is a complex disorder, resulting from an interaction between environmental and genetic factors. Several studies have addressed the association of AD with major histocompatibility complex (MHC) polymorphisms without arriving at any definite conclusions. The human leukocyte antigen (HLA) region is the key susceptibility locus in many immunological diseases. The aim of this study was to investigate the probable association between HLA-DR/DQ alleles and AD in Tunisian patients. METHODS: HLA-DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers with 55 AD patients and 100 healthy individuals serving as the control group. RESULTS: AD in Tunisian patients was found to be associated with the following alleles (Pc denotes Bonferroni corrected probability values): HLA-DRB115 (Pc < 10-3), DRB104 (Pc = 0.03) and DQB106 (Pc < 10-3). Two haplotypes found to be associated with the disease were DRB11501/DQB10602 (Pc < 10-3) and DRB10402/DQB10302 (Pc = 0.02). CONCLUSIONS: The authors believe this to be the first research linking the haplotypes DRB11501/DQB10602 and DRB104/DQB1*0302 with AD. Larger studies in other populations will be important to support the present findings of the possible susceptible risk of HLA-DR/DQ in AD.