Questionnaires were completed by 1083 nonesotropic control subjects and 170 patients with nonparalytic esotropia to determine handedness. The subjects, who had been drawn from patients attending ophthalmic clinics and private practices, were classified as right-handed, left-handed, or ambidextrous based on their answers to five questions about hand preference. Analysis of the results indicated that the handedness of patients with esotropia differed significantly from that of nonesotropic controls. The difference resulted primarily from an excess of non-right-handers among those with esotropia. Non-right-handedness is probably a marker of anomalous cerebral dominance and the disproportion of left-handed and ambidextrous subjects with esotropia may indicate that some persons with esotropia have anomalous brain architecture. In such cases, the structural anomalies might be the cause of the strabismus.