The effect of centrally administered corticotropin-releasing factor (CRF) on intraocular pressure (IOP) was investigated using the technique of ventriculocisternal perfusion. Various amounts of ovine CRF (0.01, 0.033, 0.1 and 0.33 yg/min) were perfused in conscious, male New Zealand albino rabbits for 1 hour. At a dose level of 0.1 or 0.33μg/min, CRF caused an acute IOP decrease of 2.5 mmHg, which lasted for 30 rnin. Perfusions with CRF at 0.033μg/min or higher caused delayed ocular hypotension, which oegan 20 hours after the perfusion and lasted for 2 days. Bolus intravenous injection of 3.3 yg CRF did not cause any IOP changes. These findings demonstrate that CRF can cause a centrally mediated IOP response. Superior cervical ganglionectomy eliminated the acute, not the delayed, CRF effect on IOP, indicating the involvement of ocular sympathetic nerves in the acute IOP effect.