Venlafaxine blocks the specific monoamine transporters and is devoid of significant action on muscarinic cholinergic receptors. To our knowledge, no cases of glaucoma have been reported so far. Because pain perception involves both serotonergic and noradrenergic mechanisms, venlafaxine also may be useful in neuropathic pain therapy. We report on two patients with narrow angle glaucoma affected by chronic pain. When venlafaxine treatment was begun, their ocular pressure was steadily around 17-18 mmHg. Venlafaxine was chosen (daily dose 75 mg) because this drug is claimed not to bind on muscarinic cholinergic receptors. However, 4 days later the ocular pressure of the first patient increased to 22 mmHg, which led to suspension of the drug. The ocular pressure of the second patient was 18.5 mmHg after a week, 21 mmHg after 2 weeks, and 23 mmHg after 16 days. One week after suspension, ocular pressure of the patients was 17 and 18 mmHg, respectively. Possible explanations of this ocular effect are offered: pharmacokinetic interference on the drugs used in glaucoma treatment, in vivo action on the muscarinic receptor, indirect effect via dopaminergic receptors, or direct effect on the ocular sympathetic postganglionic neurones. In any case, from a clinical viewpoint, caution should be used when giving venlafaxine to patients with narrow-angle glaucoma, and ocular pressure must be monitored.