PURPOSE: In the preinflammatory phase of S-antigen (S-ag) induced uveitis, an ocular hypotension occurs between day 2 and day 6 after S-ag injection. To better understand this phenomenon, we studied the levels of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) in the aqueous humor of S-ag injected rats at various time points after induction of disease. METHODS: Twenty-five female Lewis rats weighting 150 to 175 gm were injected in the hind foot-pad with 50 micrograms of S-antigen. IOP was measured each day at 9 am with a Tono-Pen tonometer. Aqueous humor was collected at days 0, 2, 4, 6, 9, 14 and 18 after S-ag injection. PGE2 and PGF2-alpha were assayed in the aqueous humor using an enzyme immunoassay method. RESULTS: The concentration of PGE2 increased after day 6 and peaked at day 14 after S-ag injection (45.6 +/- 9.0 mu/ml vs 1.1 +/- 0.1 mu/ml in controls, P = 0.04). The peak of PGE2 corresponded to the maximum inflammation and ocular hypertension. PGF2-alpha was increased from day 2 to day 6, with a peak at day 6 after S-ag injection (128.0 +/- 51 pg/ml vs 56 +/- 2.0 pg/ml in controls, P = 0.047), which corresponded to the preinflammatory ocular hypotension. A second peak was observed at day 18 after S-ag injection (3643 +/- 824 pg/ml, P = 0.049), which corresponded to the cessation of intraocular inflammation and ocular hypertension. CONCLUSIONS: The early increased concentration of PGF2-alpha in the aqueous humor of rats with S-ag induced uveitis may explain the ocular hypotension observed from day 2 to day 6 after S-ag injection.