The purpose of this study was to evaluate the efficacy of a novel barrier cream formulation at reducing the percutaneous toxicity of a 2xLD(50) liquid challenge of nerve agent (VX). The study was conducted in vitro and in vivo using the domestic pig. Pretreatment of the (inner ear skin) exposure site with barrier cream eliminated mortality, reduced cholinesterase inhibition and prevented any physiological or biochemical signs of intoxication. In contrast, untreated animals exposed to VX exhibited severe signs of intoxication, near total AChE inhibition and generally died within the (3 hr) exposure period (5/6 animals). Application of the barrier cream caused a significant decrease in the area of skin contaminated by VX. It was tentatively concluded that spreading was predominantly a surface phenomena (possibly mediated by capillary movement of the agent through the microrelief or between hair follicles) with little or no contribution from lateral diffusion within the stratum corneum. There was a disparity between the in vitro and in vivo skin absorption measurements that was ascribed to the absence of systemic clearance in vitro. However, both models indicated a substantial reservoir of VX within the skin, providing a potential strategy for future investigations into "catch-up therapies". In summary, the novel barrier cream formulation was effective against a 2xLD(50) (liquid, percutaneous) dose of VX applied for 3 hr. Further work should be conducted to investigate more pragmatic issues such as optimal reapplication frequency and environmental effects such as temperature and humidity.