The novel binary vehicle system consisting of ethanol (EtOH) and Panasate 800 as tricaprylin was applied to five types of nonsteroidal anti-inflammatory drugs, and its enhancing effect on drug permeation across hairless mouse skin in vitro was assessed. The permeability of all drugs was remarkably increased by the treatment of skin with EtOH/Panasate 800 binary systems compared with either EtOH or Panasate 800 alone, and the effect reached a maximum in EtOH/Panasate 800 (40/60) system. With regard to this binary system, the skin permeation ratio or flux of the drug increased in the following order: salicyluric acid (SU) > salicylic acid (SA) > alclofenac (ALC) > ketoprofen (KP) > ibuprofen (IBU). The one-layer skin model was applied concerning the above skin permeation profiles of the five drugs. Diffusion parameter (D'), partition parameter (K'), and permeation constant (Kp = D' x K') were calculated using the Laplace-transformed equations with the aid of MULTI (FILT). It was well demonstrated that the reduction of lag time and the increase of flux caused by EtOH/Panasate 800 binary vehicle systems was due to an increase of D' value by Panasate 800 and K' value by EtOH, respectively, in the skin. Especially, the EtOH/Panasate 800 (40/60) binary vehicle system produced the largest Kp value in each drug. In relation to all the EtOH/Panasate 800 binary vehicle systems, the logarithms of calculated Kp were found to be in inverse proportion to the logarithms of a n-octanol/water partition coefficient (P) of the drug which appeared in previous literature.