The purpose of the present study was to understand the skin permeation mechanism of amino acids. Skin permeation of amino acids through the excised rat skin was measured at various pH. The permeabilities varied with donor pH and amino acid. But, the permeabilities of cortisone and mannitol were almost constant in the same range of pH. It suggests that pH-dependent permeation of amino acids may be due to the different permeability of each ionic specie. The permeability coefficient of each ionic specie was estimated from the permeability-pH profiles using the dissociation constants. The estimated permeability coefficients of monocation and neutral zwitterion were not depend on the lipophilicity but on the size of the amino acids, suggesting porous mechanism of transport. The permeability coefficient was highest for dication, followed by monocation, positive zwitterion, neutral zwitterion and negative zwitterion. The electrical potential difference through the skin was too small to affect the permeability of ions. Then, the permselective property of skin seems to be caused by the difference of diffusion coefficient in pore pathway due to the hydration of ions.