The genetic factors that predispose to the development of systemic onset juvenile idiopathic arthritis (SOJIA) and its complications are not completely understood. The clinical SOJIA is different among individual patients. In the present study we have analyzed the influence of HLA-B27 and HLA-DR antigen on the disease progression, extraarticular manifestations and development of amyloidosis in 47 SOJIA patients with a long disease duration (mean 18 ±7.4 years). The main outcome measures were radiological changes, functional disability, severity of the joint disease and the presence of amyloidosis confirmed by biopsy. Each patient was graded also for severity of the systemic disease observed in the course of the disease. The statistically significant increase in the incidence of HLA-DR4 was observed in the subgroup of patients with radiological evidence of joint destruction in comparison with controls (73.7 vs. 23.6%, p < 0.0001) and patients without such changes (73.7 vs. 25%, p < 0.005) (Fig. 4). Significant differences were observed also in patients with the most severe joint disease compared with controls (63 vs. 24%, p < 0.001) (Fig. 2). Additionally, the increase in frequency of HLA-DR3 was found in patients with severe systemic symptoms persisting or recurring for more than 2 years when compared with controls (76.2 vs. 23.6%, p < 0.0001) and patients with systemic features persisting or recurring up to 2 years of the disease duration (76.2 vs. 22.7%, p < 0.001) (Fig. 1). No correlation between HLA frequencies and functional status or the presence of amyloidosis was found. Conclusion: HLA typing may be valuable for predicting joint destruction and severity of systemic manifestation of SOJIA.