The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3 +/- 17.3 microg/cm2/h. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of KT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20% and 40% of DGME, respectively. When DGME was added to PGML, the permeation fluxes were almost two times at 20-60% of DGME compared to PGML alone. In the cosolvent system consisting of propylene glycol (PG)-oleyl alcohol, the permeation rate increased as the ratio of PG increased. In the study to investigate the effect of drug concentration on the permeation rate of KT, the permeation rates increased as the drug concentration increased in all vehicles used, and the dramatic increase in permeation rate was obtained when the drug concentration was higher than its solubility. For the effects of fatty acids on the permeation of KT, five fatty acids were added to PG at concentrations of 1%-, 3%-, 5%- and 10%- caprylic acid, capric acid, lauric acid, oleic acid, and linoleic acid. The enhancing effects of fatty acids were different, depending on the concentration as well as the sort of fatty acids. The highest enhancing effect was attained with 10% caprylic acid in PG; the permeation flux was 113.6 +/- 17.5 microg/cm2/h. The lag time of KT was reduced as the concentration of fatty acids increased except for caprylic acid.