To investigate the association between HLA antigens and temporomandibular joint (TMJ) erosion, salivary composition, and focal sialadenitis in patients with rheumatic diseases.Eighty-four patients, 24 with rheumatoid arthritis (RA), 19 with mixed connective tissue disease (MCTD), 19 with ankylosing spondylitis (AS), and 22 with spondyloarthropathy (SPA) were studied. Each patient underwent clinical examination of the masticatory system, unstimulated and stimulated saliva collection, and minor salivary gland biopsy. Radiographs (OPTG) of the TMJ were obtained, and HLA allele (A, B, C and DRB1*) analysis was performed. Erosion in OPTG was scored from 0 (no erosion) to 4 (condyles totally eroded). In the analysis, scores 0-2 were grouped as normal or mild changes, and scores 3-4 as distinct erosions. One hundred healthy blood donors served as controls for HLA typing.Distinct erosion of the TMJ in OPTG was observed in 22 (27%) patients. It affected four (17%) of the 24 patients with RA, three (17%) of the 18 with MCTD, seven (37%) of the 19 patients with AS and eight (38%) of the 21 with SPA non-significant (NS). The mean erosion scores were 1.7 for RA, 1.3 for MCTD, 2.5 for SPA, and 1.6 for AS patients [probability (p) = 0.04]. The frequency of HLA-B27 antigen was higher in the AS and SPA patients, and that of HLA-DRB1*04 allele higher in RA patients than in control subjects. In the whole patient population, HLA-DRB1*01 allele was significantly associated with erosions 16/36 (44%) versus 6/46 (131%1) (p = 0.0014). In the SPA group, patients with HLA-DRBI*01 allele had a significantly higher occurrence of distinct erosions than patients without this allele [8/10 (80%) versus 0/11 (0%) (p = 0.0002)], whereas DRB1*06 was protective [0/8 (0%) versus 8/13 (62%) (p = 0.018)]. HLA-DRB1*04 was associated with increased salivary IgG in the RA patients.HLA antigens are significantly associated with the development of destructive lesions in the TMJ, as well as composition of saliva in patients with various rheumatic diseases.