Previous studies have reported that the inhalation of the alpha 2-agonist clonidine decreases airways reactivity. Other studies have shown that oral doses of clonidine acutely increase airways reactivity to histamine, but not to methacholine. Recently, a transdermal clonidine delivery system (TTS) has been approved for use, and there is an increasing interest in using this system for management of postmenopausal and smoking cessation symptoms. To our knowledge, the effects of TTS on airways function in asthmatics have not been reported. The purpose of this study was to determine if use of TTS would alter airways reactivity. Six asymptomatic asthmatic subjects underwent a baseline methacholine challenge (M). In a double-blinded randomized crossover fashion, either a placebo or a TTS patch (TTS-1, 0.1 mg/day), was applied to the arm. Four days later, the challenge was repeated. After two to three days of washout, the alternate patch was applied, and a second challenge was performed. Several days later, a second baseline challenge was repeated. This sequence was then repeated using histamine (H). The patch was well tolerated by all subjects. There was no significant change in resting pulse or blood pressure, and for the group no change in airways reactivity to either M or H was noted. In conclusion, while use of TTS-1 does not improve airways function, its short-term use in asthmatics is not associated with an increase in airways reactivity.