Transcutaneous administration of nonsteroidal anti-inflammatory drugs and essential fatty acids from fish oil, principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may simultaneously lead to increased cyclooxygenase inhibition and the production of less potent inflammatory mediators within joints. The objective of our study was to determine the permeation of ketoprofen, EPA, and DHA (from fish oil) across pig ear skin in vitro in the presence of the enhancer 1,8-cineole. Formulations containing 2.5% ketoprofen in fish oil with varying concentrations of 1,8-cineole were prepared and applied to full-thickness pig ear skin mounted in all glass Franz-type diffusion cells. Simultaneous permeation of ketoprofen and EPA and DHA from these formulations was determined by reverse phase HPLC over a 48-hr period (n = 6). We found that fish oil alone enhanced the permeation of ketoprofen across pig ear by a factor of 1.72 relative to a water vehicle. There was a dose-dependent increase in the rate of permeation of ketoprofen relative to the concentration of 1,8-cineole. The highest Q24 and Q48 was obtained with a 20% 1,8-cineole formulation with values of 355.78 +/- 50.73 microg cm(-2) and 963.29 +/- 136.69 microg cm(-2), respectively. Surprisingly, no clear effect upon the permeation of EPA and DHA by 1,8-cineole was observed, with the highest Q24 and Q48 values seen in a formulation containing no 1,8-cineole. This may have been due to differential solvation effects prior to or during the permeation process or modulation of the skin during the permeation process.