Antibodies to denatured human collagen were identified in sera of rheumatoid arthritis patients. The incidence of anti-collagen antibodies was about 60% in 100 arthritis sera and about 9% in 400 age and sex-mathched control sera. Also, the titers ranged from 1:8 to 1:512 in the rheumatoid sera, compared to a maximum of 1:4 in the controls. The occurrence of anti-collagen was shown to be independent of rheumatoid factor and was shown to be primarily of the IgG class. Both α1 and α2 chains of collagen were recognized by rheumatoid anti-collagen antibodies. Assays with five sera showed that the major antigenic determinants were cyanogen bromide fragments α1CBO, 1, and α2CB3.