Three patients with periodic fever and two with periodic fever and polyserositis (familial Mediterranean fever, FMF) were given a trial of estrogen therapy. Steroid was given either intermittently, beginning during the prodrome of febrile attacks and continuing for 1½ to 3 days, or daily to the patients with FMF. Significant suppression of symptoms occurred in two of three patients with periodic fever and marked lessening of the frequency of attacks in both patients with FMF. Improvement has been maintained for 6 to 28 months. These results suggest that anti-inflammatory and antipyrogenic properties of estrogens, which have been demonstrated previously, may be clinically useful. Additional trials of estrogen in patients with periodic fever seem warranted.