Topical application of some catecholamines to the eye can cause a transient ocular hypertensive response; a drug effect that has had various explanations. We tested the hypothesis that this effect is mediated by α-adrenoceptor stimulation and consequent contraction of extraocular muscles. We found that surgical section of three major extraocular muscles completely eliminated the initial ocular hypertensive effect and revealed an ocular hypotensive effect of topical epinephrine in rabbits. This agent is not known to cause contralateral pressure effects in normal eyes, however, in the surgically altered subjects the intact fellow eyes developed a late reduction in intraocular pressure, the significance of which remains obscure. Pupil dilatation was slightly greater in epinephrine-treated, surgically altered eyes than in normal eyes.