BACKGROUND: This study was carried out in order to improve the understanding of the pathogenesis of uveitic glaucoma. METHODS: Uveitis was induced in 48 Lewis rats by S-antigen injection. Intraocular pressure (IOP) was measured by Tono-Pen-2 daily for 24 days in 16 animals. Histopathology was performed sequentially in 14 rats on days 3, 5, 7, 9, 12, 15 and 18 after S-antigen injection. Aqueous dynamics studies were performed on days 0, 3, 7, 14 and 21. Aqueous humor production was measured using an FITC-albumin dilution technique; outflow facility was measured using anterior chamber infusion with constant pressure. RESULTS: IOP decreased to a mean of 16.5 +/- 4.3 mmHg from days 2-5 after S-antigen injections from a mean pre-experimental value of 20.5 +/- 5.4 mmHg. IOP increased from days 6 to 20 (35.8 +/- 9.1 mmHg; P = 0.00001). Histopathologic study revealed inflammation of the anterior and posterior segments from days 9 to 21 after S-antigen injection. Aqueous humor production decreased and outflow facility increased at day 3 after S-antigen injection. At days 7 and 14 after S-antigen injection, acqueous humor production was increased while outflow facility remained normal or was decreased. CONCLUSION: This model of uveitis glaucoma is characterized by three overlapping phases: (1) ocular hypertension, (2) ocular hypertension associated with clinical and histologic inflammation and (3) anatomic sequelae of uveitis and variable IOP. This model permits in vivo studies of mechanisms of IOP change associated with uveitis.