PURPOSE. Endothelin-1 (ET-1) has been found in elevated concentrations in the aqueous humor of glaucoma patients. Indirect evidence from animal studies suggests that ET-1 might directly influence intraocular pressure (IOP). The aim of this study was to determine whether ET-1 concentrations in aqueous humor of cataract and glaucoma patients correlate with IOP. METHODS. Aqueous humor and blood samples from patients with either cataract (control, n = 38), primary open angle glaucoma (POAG, n = 35), or pseudoexfoliation glaucoma (PEXG, n = 21), without other ocular or systemic disease, were collected during routine cataract surgery or trabeculectomy. ET-1 concentration was determined by an ET-1 ELISA kit. IOP was measured preoperatively by standard Goldmann applanation tonometry. All statistical analysis was performed using commercial predictive analytics software. RESULTS. Both IOP and ET-1 concentration in aqueous humor were significantly increased in POAG (23.4 +/- 6.8 mm Hg, 5.9 +/- 2.9 pg/mL) and PEXG (24.3 +/- 8.8 mm Hg, 7.7 +/- 2.1 pg/mL) compared with control (15.0 +/- 2.9 mm Hg, 4.3 +/- 2.4 pg/mL). No difference was detected for plasma ET-1 concentrations. IOP and ET-1 in the aqueous humor were significantly correlated (R = 0.394, R-2 = 0.155, P < 0.001), although no correlation was found between IOP and ET-1 in blood plasma or between ET-1 in aqueous humor and ET-1 in plasma. CONCLUSIONS. In this study, a small but highly significant correlation between IOP and the ET-1 concentration in the aqueous humor was found. Although no causative relationship can be deduced from this, ocular ET-1 effects on IOP control may merit further investigation. (Invest Ophthalmol Vis Sci. 2012; 53: 7336-7342) DOI: 10.1167/iovs.12-10216