The aim of this study was to establish whether ionized as well as un-ionized forms of certain 4-oxo-4H-1-benzopyran-2-carboxylic acids (chromone-2-carboxylic acids) with pKa values less than 2 permeated through excised human skin and, if so, to determine the permeability coefficients of the permeating species. The permeation properties of four carboxylic acids were studied as a function of concentration over the pH range 5-7 at 37 degrees C with plexiglass diffusion cells. Plots of J/CA- (the total flux due to un-ionized and ionized species obtained under steady-state conditions per unit concentration of ionized drug in the donor compartment) against CH3O+ resulted in straight-line relationships. The intercepts of these plots were shown to equal PA-, whereas the slopes multiplied by the Ka values of the compounds equalled PHA, the permeability coefficients of the ionized and un-ionized species, respectively. With all four compounds, both species were found to permeate skin, although the permeability coefficients of the un-ionized species were approximately 10(4) greater than those for the ionized species. It was demonstrated that the relative contributions of the ionized and un-ionized species to the total flux, as well as the total flux, vary significantly, depending on the pH of the drug solution in the donor cell. This may provide a means of controlling the flux of these and similar compounds through human skin.