Objective: The etiology of delusional disorder is imperfectly understood. Involvement of biological factors has long been suspected. We examined the incidence of class I human leukocyte antigens (HLAs) in patients with delusional disorder to understand the role of HLA genes and explore a possible immunogenetic etiology for delusional disorder. Methods: We used a nested case–control study design. Psychiatric reference data were available for 27 500 patients registered between 1998 and 2003. Initially, we enrolled 150 patients with delusional disorder from the India-born Bengali population, using DSM-IV diagnostic criteria. After longitudinal follow-up, 80 patients were found to have only delusional disorder, while the remaining 70 patients represented different illnesses with paranoid symptoms and were excluded. We performed serological typing on all 150 patients and applied the polymerase chain reaction–based high-resolution molecular typing method to the 80 patients with delusional disorder. Eighty healthy donors of the same ethnic background, matched for age, sex, and other socioeconomic variables, formed the control group. Results: Some of the HLA alleles were associated with delusional disorder, and the gene HLA-A*03 was found to be significantly more frequent. This gene may influence patients' susceptibility to delusional disorder. Conclusion: The study reveals important associations between HLA genes and delusional disorder. This preliminary observation may help our understanding of this disorder's genetic basis.