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Under normal conditions the stratum corneum in vivo is very much less hydrated than the excised tissue routinely used in laboratory permeability experiments. As a consequence, certain quantitative predictions of skin permeability based on laboratory experiments are not applicable to many cases of clinical and practical interest. In this study a modified in vitro permeability technique was used which permitted the hydration of the stratum corneum to be maintained very close to its natural state. Penetrant molecules were applied by adding a few microliters of acetone solution to the stratum corneum surface. The acetone quickly evaporated leaving a residue of solid penetrant. The time course of penetration of the solid material through the epidermis was observed as a function of applied dose, mild hydration, and solvent contact time. Remarkably steady, uniform penetration persisting over several weeks was observed. Generally, the penetration rates were similar to those observed in vivo and increased in a similar manner upon occlusion. Diffusion through the stratum corneum rather than sorption of the solid at the surface appears to be rate limiting. [ABSTRACT FROM AUTHOR]