To evaluate the frequency of asymmetric inferior oblique overaction and its relationship to amblyopia, the authors reviewed the records of all patients who presented to Children's Hospital of Dallas with esotropia over a 2-year period. A total of 368 patients were identified and classified as infantile esotropia, acquired accommodative or partially accommodative esotropia, or acquired nonaccommodative esotropia. Two hundred forty-two patients (66%) had no amblyopia, of which 90% had symmetric inferior oblique activity. One hundred twenty-six patients (34%) had amblyopia; of these patients, 93 (74%) had symmetric inferior oblique action. Amblyopia was strongly associated with increased inferior oblique overaction in the amblyopic eye (P less than 0.001). This finding was consistent for all subgroups. The relative risk for having amblyopia as opposed to normal vision in an eye with increased inferior oblique activity relative to the contralateral eye was 5.6 to 8.6 depending on the eye. Amblyopia should be strongly suspected in patients with esotropia and asymmetric inferior oblique activity, specifically in the eye with more inferior oblique overaction.