BACKGROUND: Pemphigus, an immunoblistering disorder, is reported with equal or near equal frequencies in men and women despite prominent female predominance in prevalence ratios of the vast majority of autoimmune diseases. OBJECTIVE: To assess a possible correlation between pemphigus and intake of sex hormones in a cohort of pemphigus patients. METHODS: A prospective online survey using a specially designed questionnaire was conducted among patients with diagnosed pemphigus in the United States during a 1-year period from September 2005 through September 2006. RESULTS: A total of 249 pemphigus cases were enrolled, 158 women (63%) and 91 men (36%). The female-to-male ratio was 1.7:1. Age at onset of the disease ranged from 16 to 85 years, mean 4.4+/-12.9 years for both sexes (not statistically significant): 45.3 for women and 45.7 for men. At the time of pemphigus diagnosis, 12% (20 of 158) of the women and 4% (4 of 91) of the men reported using hormone replacement therapy. At the time of disease onset, 46% (20 of 43) of the postmenopausal women took hormone replacement therapy. LIMITATIONS: Possible questionnaire self-reporting biases. CONCLUSIONS: The finding of a female predominance among pemphigus patients is attributed to the immunopathogenesis of the disease that makes women more susceptible to this and other autoimmune disorders and to the strikingly high proportion of hormone replacement therapy users found among postmenopausal women.