The effect of menthol on the percutaneous penetration of S(-)-propranolol (SPL) and racemic form of propranolol (RSPL) was investigated in vitro using excised abdominal skin of guinea pig. In the presence of menthol, the permeability coefficient of SPL was high compared with that of RSPL. The enhancement factors for SPL and RSPL were 2.12 and 0.85, respectively. The lag times for SPL and RSPL were reduced considerably in the presence of menthol compared to those for control (without enhancer). The present findings suggest the enantio-selective permeation of SPL across the guinea pig skin in the presence of menthol.