Changes in iron (Fe) concentration and total-iron-binding capacity (TIBC) of the intraocular fluids were measured during endotoxin-induced ocular inflammation in rabbits over a 3-week time course. In the aqueous humor, both Fe and TIBC increased to peak levels 24 h after intravitreal injection of endotoxin (10 ng) and gradually decreased to baseline levels by 3 weeks. In the uninflamed eye, the TIBC of the aqueous was only 23% saturated. During inflammation the TIBC became more highly saturated over time, reaching 50% at 3 weeks. In the vitreous humor the picture was more complicated due to the presence of slight hemorrhage. Noncellular Fe and TIBC increased to peak levels by 7 days, while TIBC approached 100% saturation. Both returned to baseline by 21 days. The influx of the partially saturated plasma protein transferrin through disrupted blood-ocular barriers most likely accounts for the increased TIBC in the inflamed eye and could provide some protection against the potentially harmful effects of Fe arising from tissue necrosis and hemolysis subsequent to hemorrhage. Under conditions of the model of inflammation studied here, the TIBC was not exceeded at any time during the 3 weeks. However, with more severe and long-lasting inflammation or when there is greater hemorrhage, the TIBC could be exceeded. This could lead to greater, and perhaps irreversible, damage to ocular tissues.