A 30-year-old black albino woman was first observed with a 4-year history of monthly urticarial episodes associated with hypereosinophilia. Hives consistently began at the end of menses and lasted for 1 to 2 weeks. A comprehensive evaluation excluded underlying malignancy and infection. There was no evidence of extracutaneous visceral involvement consistent with the primary hypereosinophilic syndrome. A 6-month prospective evaluation was performed, during which daily hive symptoms were recorded and weekly determinations of eosinophils, serum total IgE, progesterone, estradiol, and 24-hour urine histamine were obtained. Eosinophil counts (range, 4002 to 37,350 cells per cubic millimeter) increased in association with the onset of hives and decreased to baseline levels after their resolution. The 24-hour urine histamine peaked at the onset of each urticarial episode. When serum progesterone levels increased, the hives were quiescent and peripheral eosinophils decreased to baseline levels. Progesterone caused in vitro dose-related inhibition of antihuman IgE-induced histamine release from peripheral basophils of this patient. Treatment with oral medroxyprogesterone resulted in remission of urticaria and a decrease in eosinophil counts. This patient represents a unique case of chronic cyclic urticaria and hypereosinophilia that appears to be modulated by the effects of progesterone.