Allergic contact dermatitis from drugs is a significant obstacle to the development of transdermal drug delivery systems. Protocols for the sensitization of mice to drugs are needed to test methods for the prevention of allergic contact dermatitis. CBA/J female mice were sensitized to the drugs albuterol, chlorpheniramine, clonidine and nadolol by topical application. Sensitization was achieved by application of drug at 5% (w/v) to shaven dorsal skin for 5 days in a hydroxyethylcellulose vehicle. Contact sensitization was determined by measuring the ear swelling response to application of 1% drug in vehicle. Control mice treated by application of vehicle alone did not exhibit an ear swelling response to drug. Supplementation of the mice with vitamin A boosted the ear swelling response, as did application of drug to dorsal versus abdominal skin. Although plasma amounts of retinol were higher in vitamin A supplemented versus control mice, the rate of drug (albuterol and nadolol) permeation was not significantly different between vitamin A supplemented and control mice. Permeability of dorsal skin for nadolol was twice that of ventral skin, which may explain the differences in sensitization at these sites. This sensitization protocol should be useful in the development of hypoallergenic transdermal drug delivery systems.