The purpose of the present work was to find out whether there is an HLA type common to the patients who, in spite of being B27 negative, have developed reactive arthritis (ReA). We compared the HLA-antigens of 25 HLA-B27 negative ReA patients to those of healthy control persons. No statistically significant differences were observed in the HLA-A, B, C, DR and DQ antigen frequencies between the patients and the control group. The frequency of DR4 was slightly lower in the patients than in the controls, although this difference was not statistically significant. On the other hand, 18/25 (72%) of the B27-negative ReA patients experienced a chronic or prolonged course of the disease. These findings indicate that DR4 does not contribute to the chronicity of ReA in the same way that it is known to do in rheumatoid arthritis (RA) or Lyme arthritis. They do not support the hypothesis that some other HLA-antigen, in addition to HLA-B27, could have a predisposing or protective effect in ReA.