BACKGROUND Estrogen plays an important modulatory role in the immune system, and is concerned with the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA), although the mechanism has not yet been clarified. Oral tolerance, a form of specific peripheral tolerance, which is recognized as a new therapeutic strategy, is related to the function of gut-associated lymphoid tissue. METHODS In this study, using collagen-induced arthritis as an animal model of RA, the effects of 17beta-estradiol (E2) on oral tolerance induction were investigated. For induction of oral tolerance, mice were fed 60 microg type II collagen (CII) for 10 consecutive days prior to each CII immunization. Mice in the E2 treatment groups were injected with 5 microg (low dose) or 500 microg (high dose) E2 three times during the induction of oral tolerance. RESULTS Oral tolerance induction suppressed the occurrence of arthritis, the proliferative response of splenocytes to CII and the specific DTH response. However, E2 treatment abrogated the suppression, which might be connected with a change in function of Peyer's patch (PP) lymphocytes. CONCLUSIONS These results suggest that oral tolerance induction might be affected by estrogen treatment through alteration of intestinal immune responses.