The objective of this study was to determine if hyperthyroidism affects the responses of Müller's muscle to alpha-1 adrenoceptor agonists and consequently, if these responses might explain thyroid eyelid retraction. Sprague-Dawley adult rats (n = 37) were divided into control and treated groups and given either placebo or intraperitoneal triiodothyronine (250 micrograms/kg/d) for 1, 2, or 3 weeks. A suture was passed through their upper eyelid and connected to a force transducer that measured Müller's muscle contractions. Responses to phenylephrine (0.015-0.61 mmol) were compared with respect to peak amplitude and 50% duration of action. Mean maximum force values [+/-1 standard error of the mean (SEM)] in response to phenylephrine were 1.254 +/- 0.071 gr for controls and 0.963 +/- 0.062 gr for thyroid-treated subjects (p = 0.005). Mean 50% duration of response values (+/-1 SEM) were 9.143 +/- 1.108 min for controls and 5.763 +/- 0.973 min for thyroid-treated subjects (p = 0.014). Hyperthyroid rats had a significantly lower Müller's muscle response amplitude than control rats; however, duration of response was not significantly different between the groups. We believe that hyperthyroidism caused intrinsic changes in Müller's muscle that resulted in eyelid retraction. Based on hypotheses discussed in this article, we expect that further studies will localize these changes to the thyroid hormone receptor on Müller's muscle or calcium-triggered intracellular second messengers. Clinical significance would then be the ability to treat hyperthyroid eyelid retraction with drugs. This study provides the first evidence of functional impairment of Müller's muscle due to hyperthyroidism in an animal model.