We examined the sera of arthritic outbred Wistar and Sprague-Dawley rats and inbred Fisher 344 and Wistar-Lewis rats for autoantibodies to rat type I, II, IX and XI collagens following the induction of arthritis with mycobacteria (MTB). Although many sera collected over an extended time were assayed in addition to acid eluates of arthritic joints, convincing evidence for autoimmunity to collagen could not be demonstrated. Instead, modest non-specific reactions were observed to collagen, irrelevant proteins, and buffer-treated plastic microtitre wells. In contrast, antibodies to purified protein derivative (PPD) were detected in the sera of rats developing adjuvant-induced arthritis, and antibodies to type II collagen, in the sera and joint eluate of rats developing experimental collagen-induced arthritis. Lastly, delayed-type hypersensitivity responses to collagen could not be detected, nor could adjuvant-induced arthritis be attenuated by soluble collagen injected intravenously before challenge with MTB. We conclude that adjuvant-induced arthritis and experimental collagen-induced arthritis are distinct models of rheumatic disease and that autoimmunity to collagen is neither prevalent in adjuvant-induced arthritis nor necessary for its pathogenesis.