In order to develop a basic concept of the permeability of the human nail plate and thus create a better understanding of the toxic potentials and therapeutic possibilities of substances applied to the nail, avulsed cadaver nails have been placed in specially constructed diffusion chambers and their permeation by water and the n-alkanols through dodecanol, all in high aqueous dilution, has been investigated. The permeability coefficient of water is 16.5 X 10(-3) cm h-1 and that for methanol is 5.6 X 10(-3) cm h-1. Ethanol's permeability coefficient measured 5.8 X 10(-3) cm h-1. Permeability coefficients decreased systematically thereafter to a low value of 0.27 X 10(-3) cm h-1 at n-octanol. The middle chain length alkanols, n-pentanol through n-octanol, have similar permeability coefficients but n-decanol and n-dodecanol show higher rates of permeation. The data suggest that, as a membrane, the hydrated human nail plate behaves like a hydrogel of high ionic strength to the polar and semipolar alcohols. Declining permeability rates appear linked to decreased partitioning into the complex matrix of the plate as the compounds become hydrophobic. The results for n-decanol and n-dodecanol introduce the possibility that a parallel lipid pathway exists which favours the permeation of these exceedingly hydrophobic species.