Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system originated by a complex interplay of environmental and genetic factors. The association of MS with the human leukocyte antigen (HLA) class II alleles was investigated in MS patients in northwest Greece, in the geographical region of Epirus.Our aim was to estimate the prevalence of the HLA-DRB1*1501, HLA-DQB1*0602 and HLA-DQA1*0102 alleles, consisting the most common susceptibility haplotype in North European and North American Caucasians.We studied 126 MS patients and 93 age and sex matched healthy controls. HLA typing was performed by a polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP) method.We found that HLA-DRB1*1501, HLA-DQB1*0602 and HLA-DQA1*0102 alleles were significantly more frequent among patients (34% versus 11%, p=0.00015; 69% versus 51%, p=0.01; 76% versus 55%, p=0.002, respectively). HLA-DRB1*1501, HLA-DQB1*0602, HLA-DQA1*0102 haplotype was significantly more common among patients (p=0.00067). HLA-DRB1*1501 and HLA-DQB1*0602 alleles were more frequently detected in patients with initial symptoms from the brainstem or the cerebellum (p=0.024). No significant correlation was observed among these alleles with sex, disease clinical course, or age at onset.This is the first study to investigate genetic susceptibility to MS in Greece. Our results are in line with previous reports in North European and North American patients.