Antibodies to native chick and bovine Type II collagen were measured by radio immunoassay, in 83 rheumatoid arthritis (RA) patients and 14 normal controls. Anti-chick Type II collagen and anti-bovine Type II collagen antibodies were found in 48% and 43% of RA patients, respectively. A strong correlation of antibodies to chick and antibodies to bovine collagen was described, suggesting cross-reactivity between different collagen species. There was an association between the presence of anti-native Type II collagen antibody and the expression of HLA-DR2. It is suggested that the production of anti-collagen antibody may be under genetic control in RA, but not associated with the major genetic marker of disease susceptibility, HLA-DR4.