Chronic spontaneous urticaria (CSU) is the most common form of chronic urticaria. A considerable amount of data supports an immunological basis for CSU. Some research has focused on the association between chronic urticaria and specific human leukocyte antigen (HLA) alleles. The aim of this study was to investigate the HLA status of Polish patients diagnosed with CSU. <i>Methods:</i> The standard complement-dependent microlymphocytotoxicity assay and PCR amplification with sequence-specific primers were used to analyze HLA alleles in 115 patients diagnosed with CSU, and the results were compared to those from 162 healthy, genetically unrelated individuals. <i>Results:</i> Among the HLA-A alleles, A-33 occurred significantly more often in the control group (p < 0.01). Analysis of the HLA-B allele frequencies revealed the prevalence of the B44 antigen in the study group (p < 0.0001). Frequencies of HLA-C alleles and HLA-DQ did not differ significantly between the groups. Among the HLA class II alleles, DRB1*04 was observed significantly more often in the study population (p < 0.001), mainly in the autoimmunological subtype of urticaria. <i>Conclusion:</i> HLA alleles may be involved in CSU development or play a protective role in CSU.