The permeation of naproxen through excised human skin and isolated perfused rabbit ear skin has been determined. It was found that both Azone and capsaicin enhanced the permeation with an enhancement ratio of up to 4-fold. The magnitudes of the effect were similar in human and rabbit skin. The permeation of naproxen from a saturated solution of the drug through skin pre-treated with Azone was similar to that from a commercial preparation (Naprosyn). In the perfused rabbit ear experiments the presence of capsaicin had no effect on the vasodilatation of the blood vessels, inferring that the penetration enhancement was a direct result of capsaicin influencing the barrier function of the skin. Structural similarities between Azone and capsaicin were seen using molecular graphics.