Background: The methylphenidate transdermal system (MTS) (Daytrana [Shire Pharmaceuticals Ireland Ltd., Wayne, PA]) has been shown to be well tolerated and effective; however, skin reactions, typically redness and itching, have also been noted with MTS use. Objective: The purpose of this study was to determine the irritancy threshold of methylphenidate (MPH), the active ingredient in the MTS, in healthy adults for use in subsequent patch testing. Methods: This was an open-label single-site pilot study. Eligible subjects had MPH (six different concentrations in two vehicles) patch tests applied to the paraspinous region of the upper back. Subjects returned after 48 hours and 96 hours for investigator assessments of each reaction. Results: All enrolled subjects (n 5 20) completed the study. There were no definite positive reactions in any subject at any test concentration. Overall, doubtful (macular erythema) reactions were noted on 12 sites at the 48-hour reading and on 6 sites at the 96-hour reading. With both aqueous and petrolatum vehicles, more doubtful reactions were noted at the lower MPH test concentrations. Conclusion: When performing patch testing to confirm possible allergic contact dermatitis from topical MPH, several test concentrations in the low-to-middle range (such as 0.1%, 1%, and 10%) prepared in petrolatum are advisable.