PURPOSE. TO determine the effect of moderate zinc deficiency on antioxidant defenses and measures of oxidative stress in the retina and retinal pigment epithelium (RPE) of Brown Norway Rats. METHODS. Twenty-four rats were housed individually and divided into three groups of 8 rats each. Group 1 was fed ad libitum a semipurified control diet formulated to contain 50 parts per million [ppm] total zinc; group 2 was fed ad libitum an identical diet but containing 5 ppm total zinc; and group 3 was pair-fed the control diet but restricted in amount to that consumed by group 2. Food intake was measured daily and the rats weighed weekly. After 6 weeks, the rats were killed and the following measurements were made: serum zinc, serum alkaline phosphatase, retinal zinc, RPE choroid zinc, RPE-choroid catalase, liver metallothionein (MT), retinal MT, RPE-choroid MT, retinal catalase. and retinal thiobarbituric reactive substances (TBARS). RESULTS. The following showed statistically significant differences between groups 2 and 3, respectively: serum Zn (1216 mu g/l versus 1555 mu g/l, P less than or equal to 0.01), serum alkaline phosphatase (3.75 U/mg versus 5.10 U/mg, P less than or equal to 0.05), liver MT (4.3 mu g/mg protein versus 16.7 mu g/mg, P less than or equal to 0.0001), RPE-choroid MT (1.3 mu g/mg protein versus 2.2 mu g/mg, P less than or equal to 0.02), retinal MT (0.85 mu g/mg protein versus 2.8 mu g/mg, P less than or equal to 0.05), and retinal TEARS (6.2 nM/mg protein versus 2.2 nM/mg, P less than or equal to 0.05). CONCLUSIONS. The results show that retinal MT and RPE MT concentrations are very sensitive to intake of dietary zinc. The increase in retinal TBARS in group 2 indicates that moderate zinc deficiency increases oxidative stress to the retina. The results also suggest that MT is protective against lipid peroxidation of retinal membranes.