This study was designed to clarify the relationship between the properties of propiverine and skin penetration, and to compare the in vitro penetration characteristics of propiverine and terodiline through rat skin. Propiverine in both hydrochloride and free forms penetrated across the skin extremely slowly, with a 2.6 times higher flux in the hydrochloride than that in the free base, in the absence of enhancers. Various enhancers failed to enhance the penetration of propiverine hydrochloride, whereas the same agents slightly increased the flux of the free form, these being due to the slow release rate of the free form from the gel formulations, an extremely high lipophilicity (log Poct/water > 4.97), much less solubility (0.141 mg/ml) and a large partition capacity of the drug to skin components. Terodiline in both forms was able to rapidly penetrate through the skin, even in the absence of enhancers, with 20.2 and 9.8 times higher fluxes respectively, than the corresponding forms of propiverine. The high penetration characteristics of terodiline would be due to a suitable lipophilicity, low binding property as well as the structural masking from the binding to the epidermal components. Propiverine hydrochloride penetrated through the stratum corneum 4.4 times and viable skin 3.1 times higher than through full-thickness skin, while the fluxes of terodiline through the stratum corneum and viable skin were similar to each other, with high penetration rates for each form.