Certain human lymphocyte antigen (HLA) haplotypes have been correlated with the presence of certain diseases. To date no significant relationship between periodontitis and HLA haplotype has been demonstrated. The purpose of this study was to determine the frequency of HLA-A, HLA-B and HLA-C haplotypes in patients resistant to chronic periodontitis and to determine if there is any association between specific HLA genes and periodontal health. Twenty-five healthy individuals who demonstrated a high resistance to periodontal disease (mean age 49.9 years) were matched to 25 subjects with chronic periodontitis and to a periodontally undiagnosed population of 22,000 individuals. Peripheral blood was taken and HLA specificity was determined by the microlymphocytotoxicity test. The results indicated a statistically significant increase in the occurrence of HLA-B5 (P = 0.0059) and a trend in the occurrence of HLA-A28 (P = 0.0565) in those patients resistant to periodontal disease when compared to the matched controls. When compared to the large random control group, a significant correlation was observed for HLA-A28 (P less than 0.01) in blacks and HLA-B5 (P less than 0.01) in whites. It is possible that the HLA-A28 and the HLA-B5 individual may have the ability to resist the progression of chronic periodontitis.