OBJECTIVE: To determine whether work performed with the arms in a highly elevated position is associated with alterations in the rotator cuff tendons as assessed by magnetic resonance imaging (MRI). METHODS: A cross-sectional study was performed in a historical cohort of male machinists, car mechanics, and house painters. The participants were right-handed, ages 40-50 years, and had been employed in their trades for not less than 10 years. Seventy-one percent of invited subjects participated (136 of 192). Lifetime upper arm elevation was assessed by direct measurements combined with individual work histories obtained by questionnaire and from registry data. Supraspinatus tendinopathy was evidenced by MRI signal intensity changes and morphologic alterations. Infraspinatus and subscapularis tendinopathy were also assessed. Additional outcomes were acromioclavicular joint degeneration and humeral head cysts. The MRI findings were evaluated by radiologists who were blinded to exposure status and symptoms. RESULTS: An exposure-response relationship was found between lifetime upper arm elevation and supraspinatus tendinopathy, with an age-adjusted odds ratio of 1.27 (95% confidence interval 1.02-1.60) for a 5-month increase in the total number of full-time working months spent with the arm elevated >90 degrees . CONCLUSION: Work with the arms in a highly elevated position is associated with MRI-diagnosed alterations in the supraspinatus tendon. By demonstrating the first part of a possible biologic pathway, the study corroborates the work-relatedness of rotator cuff disorders.