Evidence has suggested a genetic link between the HLA-DR4 phenotype and rheumatoid arthritis (RA), particularly in its seropositive form. Such an association varies among different ethnic groups and remains controversial for seronegative patients. Data obtained for a group of 64 Chilean patients with RA (46 seropositive, 18 seronegative), as defined by the 1987 criteria of the American Rheumatism Association, and for 76 controls are reported here. The prevalence of HLA-DR4 and DR9 was significantly increased in the group of patients considered as a whole. The prevalence of HLA-DR4 was not significantly higher, however, when seronegative and seropositive patients were separately compared with controls. Also, it did not correlate with the severity of the disease within each subgroup of patients. On the other hand, HLA-DR9 showed a highly significant difference, not previously described, only for the seropositive patients in comparison with controls. The prevalence of DQ specificities showed no relevant differences among the groups. The HLA-DR4 serotype, therefore, is a weak marker for RA and does not differentiate any subgroup of patients in the Chilean group studied. This new finding, indicating an association between RA and the DR9 antigen, may be explained by the suggestion that susceptibility epitopes are shared among different DR molecules. This hypothesis might also account for the variation in the association of DR4 with RA.