Sodium hydroxide-induced irritation was studied in 34 volunteers, by means of 24-h patch testing at different concentrations, and by a 10-min testing procedure employing 0.1 mol/l NaOH. As a supplement to subjective evaluation of skin changes, assessments of test areas by TEWL measurement and sonography were performed at 24, 48 and 72 h. After 24-h patch testing, instrumental evaluations showed an increase in the extension of the hypo-echogenic dermal area and in TEWL, whereas a 10-min NaOH application induced a decrease of the dermal and epidermal reflectivity and an increase in TEWL. Twenty-four hour patch testing with 4% NaOH allowed a classification of subjects into two categories: subjects who reacted normally and hyper-reactors. Hyper-reactors showed an enhanced inflammatory response and a more pronounced barrier function damage, as assessed clinically and instrumentally by decreased dermal reflectivity, and by higher postexposure TEWL. Subjects with a more marked inflammatory response to 4% NaOH also showed greater TEWL increases during the short-term testing procedure employing 0.1 mol/l NaOH. Moreover, these subjects were characterized by higher baseline TEWL values, indicating that cutaneous reactivity to NaOH is at least partly correlated to impaired stratum corneum function, which is inadequate to effectively prevent compounds from penetrating the skin.