OBJECTIVE The authors determined the levels of the secreted, interstitially located extracellular superoxide dismutase (EC-SOD), the cytosolic copper- and zinc-containing SOD (CuZn-SOD), and the mitochondrial manganese-containing SOD (Mn-SOD) in tears, cornea, sclera, aqueous humor, lens, vitreous body, and retina of the human eye. METHODS SOD enzymatic activity was determined by the direct spectrophotometric method using KO2. The amounts of EC-SOD and CuZn-SOD protein were also determined using enzyme-linked immunosorbent assay. RESULTS Tears, aqueous humor, and vitreous body contained little SOD activity. Here ascorbate is the major scavenger of superoxide radicals. Of the ocular tissues studied, the lens contained the least SOD activity, 15-fold less than that of the average human tissue. The majority came from CuZn-SOD, but the lens also contained considerable amounts of inactive enzyme. There was some Mn-SOD, but the EC-SOD content was negligible. The cornea and sclera contained several times more SOD activity than the lens, and the EC-SOD contents were equal to or larger than those of CuZn-SOD. The retina contained much CuZn-SOD activity, but the EC-SOD and Mn-SOD activities were low. CONCLUSIONS Ocular tissues and fluids, except for those in the retina, are less protected against superoxide radicals than extraocular tissues and fluids. The large amounts of EC-SOD in the sclera and cornea may be related to the risk for photochemical production of superoxide in these tissues. If inflammatory reactions occur, ocular tissues are at risk for damage induced by superoxide radicals and peroxynitrite, the reaction product with nitric oxide.