An exactly defined group of 102 German patients suffering from Adult Periodontitis (AP) was investigated for its markers HLA-A, B, Cw, DR, and DQ. For this purpose, not only serologic techniques (MLCT) were use, but additional molecularbiologic methods (PCR-SSP). In contrast to all previously performed international studies the patients were not compared with periodontologically undifferenciated blood donors (expressing so-called "normal distribution"), but with a control group consisting of 102 elder probands clinically free of periodontis ("resistant") In parallel a periodontitis group consisting of 50 patients with rapid progredient periodontitis and 100 patients witth adult periodontitis was combined and compared with the group of probands free from periodontitis. AP patients showed significantly increased associations with the HLA markers A*11, A*29, A*33, B*14 (B64/65), and Cw*08 as well as a negative association with HLA-A*03. There were no gender effects. In the common group of patients having periodontitis the same significantly increased associations occurred with HLA-A*11, -A*29, -B*14 (64/65), whereas a negative association of the markers HLA-A*31 and -A*(30/31) was striking just in this group, but not in the AP group. Surprisingly, a significantly increased frequency of homozygositiy of HLA-DRblank (non DRB3/4/5) was revealed in the "resistant" group. The estimated haplotypes associated with HLA-B*14 are considered to be susceptible with AP. HLA-A*03 positive combinations, however, are more representing resistance to AP. It is striking that an unusual association of the class II marker HLA-DRB1*04 with the ancestral haplotype HLA-Cw*08:B*14 occurs only in groups of probands having AP or IgA deficiency. It can be suggested that there is an influence by individual HLA markers as well as by their combinations on the formation of AP or inflammatory periodontal diseases in general. This effect can be explained by crossreactivity between HLA antigens and microbes (molecular mimicry) or HLA-depending immune response against bacterial antigens.