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No studies have been performed evaluating skin barrier alterations in humans exposed to ultra-low humidity (ULH) in spite of several lines of evidence from animal experiments suggesting that the skin barrier is altered on exposure to ULH. The objectives of this study were to assess barrier function changes in workers occupationally exposed to ULH (relative humidity 1.5%), and to evaluate whether the exposure duration shows a dose-response relationship with transepidermal water loss (TEWL) and skin capacitance. A total of 49 male workers exposed to ULH for 12 h per working day were classified into five subgroups based on their ULH exposure duration (<0.5 months, 0.5-1.0 month, 1.1-10.0 months, 10.1-20.0 months, and >20.0 months). A group of 12 age-matched male laboratory workers from a normal humidity environment were recruited as a control group. TEWL and skin capacitance were measured to evaluate their skin barrier function. TEWL measurements showed a significant decline (8.3±0.4 vs 10.0±0.4 g m−2 h−1, P<0.05) but no differences were found in skin capacitance (39.7±1.3 a.u. vs 45.0±2.4 a.u., P=0.68) between the whole ULH exposure group and the control group. Maximum decreases in TEWL and skin capacitance were seen in the subgroups exposed for <0.5 months and 0.5-1.0 month, respectively. Almost completely natural recovery occurred in skin capacitance after 20 months ULH exposure, in contrast to less than 90% recovery in TEWL. Three stages were defined according to the pattern of alterations in TEWL and skin capacitance in relation to ULH exposure duration. A positive association between TEWL and skin capacitance occurred in the control group and stage I but a negative correlation in stage II. No correlation was found in stage III. Our study demonstrated that workers exposed to a ULH environment could exhibit skin barrier alterations. Both TEWL and skin capacitance decreased within 2 weeks of ULH exposure. The maximum alterations in TEWL and skin capacitance occurred during 0.5-1.0 months and 2 weeks, respectively. TEWL recovered partially and more slowly than skin capacitance which recovered earlier and almost completely.