The influence of the chemico-physical nature of the vehicle on the skin penetration of topically applied drugs was evaluated in vivo. Five different ointment formulations containing nicotinate esters as model penetrants were tested on human skin. The degree of drug penetration allowed by the various formulations was revealed by means of the erythema induced by the drug, detected by a X-Rite tristimulus reflection colorimeter. The excipient influenced the penetration of the nicotinate esters used to various extents. The concentrations of the tested drugs were found to be an important factor influencing drug penetration and persistence of erythema.