Disease course and HLA antigens were determined in 29 patients with definite and 13 patients with probable adult-onset Still's disease (AOSD). Twenty-six patients had persistent disease with continuous disease activity for at least 1 year. Radiographic examination revealed evidence of joint destruction in 26 patients. In 15 patients, at least 1 root joint was impaired. The frequency of DR4 was increased in the total group of patients (35%, P = 0.03) and in the 29 patients with definite AOSD (41%, P = 0.02) compared with the frequency in normal controls (20%). None of the patients was positive for DR1, and only 1 was positive for Bw35. The frequency of DRw6 was increased in the patients with involvement of at least 1 root joint (40%, P = 0.03) compared with the patients without involvement of these joints (11%).