We examined the T-non-T cell autologous mixed lymphocyte reaction (AMLR) of spleen cells from rats with arthritis induced by Freund's complete adjuvant in an effort to establish an animal model for the study of the relationship between the AMLR and autoimmune disease. We found that the splenic T-non-T AMLR was markedly decreased in rats with adjuvant-induced arthritis and that this decrease was mediated by suppressor cells within the nylon-wool-adherent stimulator cell population. However, we also found a similar decrease in the AMLR of arthritis-resistant Fisher 344 rats that received Freund's complete adjuvant but did not develop arthritis. Control animals with local inflammation induced by turpentine, a non-arthritogenic inflammatory substance, had normal AMLR, whereas other controls given Freund's incomplete adjuvant, also a non-arthritogenic substance, had a modest responder cell-mediated decrease in AMLR. These studies help to clarify the relationship between the decreased AMLR and the pathogenesis of adjuvant-induced arthritis by demonstrating that: 1) the acute-phase inflammatory response does not reduce the AMLR; and 2) the decreased AMLR can occur in the absence of overt autoimmune disease. This latter observation calls into question the proposed pathogenetic relationship between the AMLR and autoimmune disease states.