The effects of 17 beta-oestradiol and progesterone on the development of type II collagen-induced arthritis (CIA) and the anti-type II collagen (CII) autoantibody response were investigated. Treatment with physiological doses of 17 beta-oestradiol, inducing serum levels below the estradiol peak at the end of pregnancy, abrogated the development of arthritis and suppressed the anti-CII autoantibody response. Treatment with progesterone alone did not have significant effects on the development of arthritis or on the anti-CII autoantibody response. However, a combined treatment with both progesterone and oestrogen in physiological doses induced a more pronounced suppression of CIA than the suppression induced with oestrogen treatment alone. These findings suggest that oestrogen, but not progesterone, may be the critical factor to explain the pregnancy-related down-regulation of CIA.