Using electron microscopy, we investigated the effect of (i) a dilute surfactant and of water alone on the ultrastructure of stratum corneum lipids in pig skin exposed in vitro at 46 degrees C, and (ii) of water alone on human skin exposed in vivo at ambient temperature. For pig skin, the surfactant sodium dodecyl sulfate disrupts stratum corneum intercellular lamellar bilayers, leading to bilayer delamination and "roll-up" in a water milieu after 1 h, extensive bilayer disruption after 6 h, and nearly complete dissociation of corneocytes after 24 h. Corneodesmosomes show progressive degradation with exposure time. Water alone also disrupts the stratum corneum, but with a slower onset. Alterations in intercellular lamellar bilayers, but not intercellular lamellar bilayer roll-up, are detected after 2 h. Intercellular lamellar bilayer roll-up occurs after 6 h. Extensive dissociation of corneocytes occurs after 24 h of water exposure. Unlike sodium dodecyl sulfate, water exposure results in the formation of amorphous intercellular lipid. Corneodesmosome degradation parallels intercellular lamellar bilayer disruption; calcium appears to offer some protection. Similar disruption of intercellular lamellar bilayers occurs in human skin in vivo at ambient temperature. Our studies show that water can directly disrupt the barrier lipids and are consistent with surfactant-induced intercellular lamellar bilayer disruption being due at least in part to the deleterious action of water. Intercellular lamellar bilayer disruption by water would be expected to enhance permeability and susceptibility to irritants; accordingly, increased attention should be given to the potential dangers of prolonged water contact. For common in vitro procedures, such as skin permeation studies or isolation of stratum corneum sheets, exposure to water should also be minimized.