Pemphigus is a severe, autoimmune, blistering disorder with a high incidence among young women in rural Tunisia. The authors investigated explanatory environmental factors. A multicenter case-control study was conducted prospectively from 1992 to 1996 in Tunisia. Sixty-eight incident female cases of pemphigus and 166 controls matched on age, hospital, and geographic area were included. Data collected concerned socioeconomic status, medical history, drug intakes, lifestyle, and environment. Several factors were significantly associated with pemphigus in multivariate logistic regression analyses: traditional cosmetics (odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.1, 14.8); Turkish baths (OR = 3.2, 95% CI: 1.4, 7.3); cutting up raw poultry (OR = 5.1, 95% CI: 1.3, 19.4); contact with ruminants (OR = 2.7, 95% CI: 1.3, 5.8); and wasp, bee, and spider stings (OR = 3.1, 95% CI: 1.5, 6.4). A dose-dependent relation was observed for traditional cosmetics. All risks except insect bites were higher when analysis was restricted to younger women, the demographic group with higher incidence. The strength of the associations, the dose-dependent relation for traditional cosmetics, and the increase of risk estimates for younger women support a causal relation. Traditional cosmetics widely used by Tunisian women could play a major role in excess of cases of pemphigus.