HLA proteins are genetically determined, and account in part for individual immune response. Several studies have been performed seeking an association between HLA antigens and various forms of periodontitis with no conclusive results. The aim of the present study was to determine the frequency of HLA antigens of patients suffering from the localized (LJP) and the generalized (SGP) forms of early-onset periodontitis (EOP). Twenty-six EOP patients from the same ethnic group were studied in comparison to 113 race-matched controls. The EOP group included 11 LJP and 15 SGP patients. HLA-A9 and B15 antigens were found to be significantly elevated in the patient group. These differences were found to be due to the high frequency of A9 and B15 antigens in the SGP patients, with the LJP patient group showing no significant difference from the control group. The results are in agreement with previous studies in which A9 and B15 were found to be associated with EOP. However, previous studies did not differentiate between the localized and the generalized form of EOP. These results support the hypothesis that the generalized and the localized forms of EOP are under different genetic control.