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Background: Vulvitis that is refractory to all treatment remains a therapeutic challenge. Hypersensitivity to progesterone and estrogen has been recognized as a rare cause of premenstrual dermatoses. Such hypersensitivity seemed to be the cause of vulvitis in the patients described below., Cases: Nine women had treatment-resistant cyclic vulvitis and two patients had vulvitis develop after commencing hormone replacement therapy (HRT). These patients demonstrated delayed-type hypersensitivity responses by intradermal testing to endogenous estrogens, with two of the patients also reacting to intradermal testing with progesterone. A group of 19 healthy control subjects with no history of vulvar symptoms did not react to any test substance. Ten subjects with other vulvar dermatoses also did not react to any test substance. Of the nine patients with cyclic vulvitis, one recovered at menopause, and three responded to therapy aimed at lowering endogenous estrogen levels. One was able to control symptoms with a potent topical corticosteroid, and four elected not to be treated. Both patients with HRT-related vulvitis recovered when HRT was ceased., Conclusion: Hypersensitivity to estrogen appears to be implicated in chronic, cyclic vulvitis and vulvitis related to HRT in these patients. This is the first report of vulvitis due to estrogen hypersensitivity. The problem may not be rare and should be considered in patients with unexplained cyclic vulvitis unresponsive to standard therapy or in those developing noncandidal vulvitis on HRT. Specific therapy aimed at suppressing or antagonizing estrogen may be required in these patients.