Variation in the DQB 1 locus of the HLA gene, Which is involved in immune responsiveness, has been reported in some patients with early-onset periodontitis (EOF). The purpose of this study was to examine the distribution of subjects with gene variation at the HLA-DQB 1 locus of a series of patients with periodontitis and healthy donors to confirm a previous study. The subjects were 40 patients with periodontitis (20 EOF patients and 20 adult periodontitis [AP] patients) and 40 periodontally healthy donors. In order to detect gene variation in the DQB 1 fragment, we used the restriction fragment length polymorphism method on the 1 kb-DNA fragment, including the third exon of DQB 1, amplified by the polymerase chain reaction method. Gene variation was found in 14% (11/80) of the subjects. Seventy-three percent (8/11) of the subjects with gene variation were suffering from periodontal disease, and 88% (7/8) of periodontitis patients having gene variation had EOP. Three healthy donors with the gene variation were found, however, all of them were blood relatives of the EOP patients examined. Its prevalence was significantly higher (p<0.05) in EOF patients than in the AP patients and healthy donors. This coincidence suggested that the hereditary gene variation in HLA-DQB 1 partially explains the pathogenesis of EOP.