Zinc is an essential trace metal, but many aspects of its toxicity remain unclear. In this study, we investigated zinc effects on oxidative stress parameters and antioxidant profile in four tissues (gill, liver, kidney, and white muscle) of Fundulus heteroclitus. Possible interactive effects of salinity were also studied. Killifish were exposed to sublethal level (500 μgL(-1)) of waterborne zinc for 96 h in 0% (fresh water), 10% (3.5 ppt), 30% (10.5 ppt) and 100% sea water (35 ppt). Salinity per se had no effect on any parameter in the control groups. Zinc exposure clearly induced oxidative stress, and responses were qualitatively similar amongst different tissues. Salinity acted as a strong protective factor, with the highest levels of reactive oxygen species (ROS) and greatest damage (protein carbonyls, lipid peroxidation as indicated by thiobarbituric acid reactive substances (TBARS) in 0 ppt, the least in 100% sea water (35 ppt), and gradations in between in many of the observed responses. Increases in total oxidative scavenging capacity (TOSC) occurred at higher salinities, correlated with increases in the activities of superoxide dismutase (SOD) and glutathione-S-tranferase (GST), as well as in tissue glutathione (GSH) concentrations. However, TOSC was depleted in zinc-exposed fish at 0 ppt, accompanied by decreases in SOD, GST, GSH, and also catalase (CAT) activity. Our results confirm that sublethal waterborne zinc is an oxidative stressor in fish, and highlight the important protective role of higher salinities in ameliorating the oxidative stress associated with zinc toxicity in this model estuarine teleost.