The enhancement of model hydrophilic (propranolol hydrochloride) and lipophilic (diazepam) drug penetration across rat and hairless mouse skin in vitro has been studied. Preliminary experiments established that most n-alkanes having chain lengths of between 7 and 16 promote the flux of both drugs. For propranolol, enhancement varied parabolically with carbon number; for diazepam, heptane was ineffective and all others were essentially equipotent. Enhancement by n-nonane was then compared with that by n-nonanol. Propranolol flux was increased by both enhancers, whereas diazepam penetration was not affected by the less lipophilic alcohol. The enhancement of propranolol by n-nonane and n-nonanol was examined as a function of adjuvant concentration in the applied formulation. Maximum increases in maximum penetration rates of 6.5-fold (n-nonane) and 8.2-fold (n-nonanol) were determined. As expected, the enhancement was saturable, indicative of a maximally perturbed stratum corneum. Finally, the penetration enhancing abilities of six monoterpenes were assessed. The purely hydrocarbon analogues promoted both propranolol and diazepam transport to an extent similar to that of n-nonane. The terpenes with hydrogen-bonding ability, however, only enhanced propranolol flux (at a level comparable to n-nonanol). While the data reported do not directly reveal mechanistic information on percutaneous penetration enhancement, they do provide a starting point for the rational investigation of interrelationships between drug, enhancer, and skin. Such information is clearly essential for the optimization and exploitation of transdermal drug delivery.