After repeated contact, many surfactants will cause skin irritation and, especially, dryness and scaliness. Earlier in vitro investigations suggested that the irritation potential of anionic surfactants was related to the induction of hydration of isolated stratum corneum membranes. We have now investigated early surfactant-stratum corneum interaction in vivo. Sodium salts of n-alkyl sulfates with variable carbon chain length (n = 8-14) were tested for the promotion of stratum corneum hydration by measurements of skin surface water loss and electrical capacitance measurements in healthy adult human volunteers. The surfactant-induced increase in water uptake was confirmed in vitro by means of isolated stratum corneum samples and surfactant solutions labeled with tritiated water. In a parallel experiment the irritation potential of these compounds was investigated by 24-h patch testing in human volunteers. The irritant responses were quantified non-invasively by erythema (skin color reflectance measurements) and transepidermal water loss measurements. Hydration of stratum corneum exposed for 5 min to surfactant solutions significantly exceeded that of controls (phosphate-buffered saline). It increased with application time and was concentration dependent, saturable with increasing concentration, and rapidly reversible. Baseline hydration was re-established only 10-15 min after treatment termination. Induction of hydration was closely correlated with the irritation potential of the investigated compounds. It initially increased with increasing carbon chain length. The maximum response was obtained for the C12 analogue (sodium lauryl sulfate). With further increases in molecular size induction of stratum corneum hydration subsequently decreased. We have demonstrated that anionic surfactants increase stratum corneum hydration in vivo. The present results suggest that the mechanisms responsible for the hydration are related to the irritation properties of these compounds.