Antibody activity against collagen was measured in 53 samples of serum from 48 patients with active signs of epidemic polyarthritis (EPA) following infection with Ross River virus. Activity was higher against denatured collagen than against native collagen, but was within the normal range for each. Determination of HLA phenotypes permitted a search for any relationship between HLA type and differences in collagen antibody levels within the normal range. No relationship was detected with HLA antigens predominating in EPA or with HLA antigens that are associated with high collagen-antibody levels in rheumatoid arthritis (RA), which suggests that the latter associations may represent failure to control collagen antibody levels after the onset of RA. The findings also provide evidence against a role for nonspecific enhancement of humoral immune responses in the pathogenesis of EPA, and constitute a further point of distinction between EPA and RA.