The skin permeation enhancement of papaverine hydrochloride by free fatty acids (C3-C12), monoglycerides (side chains C5-C12) and caprylic acid (C8) esters was evaluated using the excised hairless rat skin. Enhancement was marked in the case of glyceryl monocaprylate; the cumulative amount of papaverine that permeated through skin over 28 hours from an aqueous suspension was 29.7 mg/cm2 with, and 26.9 micrograms/cm2 without glyceryl monocaprylate. The mechanism of enhancement was studied by measuring the effect the enhancers had on the diffusion and partition parameters of papaverine. Free fatty acids mainly affected the drug's diffusion, and monoglycerides mainly affected the drug's partition. For monoglyceride enhancers, a good linear relationship between the flux of papaverine and the amount of enhancer in skin was established. n-Octanol-water partition coefficients (log Pcal) of the enhancers were selected as indicators of their physicochemical properties, and related to their penetration-enhancing abilities. A parabolic relationship was found between the log of the flux of papaverine and log Pcal, for all types of enhancers. The relationship may be a good indicator in predicting enhancing effects.