We investigated the effects of Zn, Cd and a Zn + Cd mixture on antioxidant parameters and metal accumulation in Oreochromis niloticus. Fish were exposed to 0.5 and 5.0 mg l(-1) Zn, 0.1 and 1.0 mg l(-1) Cd, and 0.5 mgl(-1) Zn + 0.1 mg l(-1) Cd and 5.0 mg l(-1) Zn + 1.0 mg l(-1) Cd mixtures for 7 and 28 days to determine Zn and Cd accumulation, reduced glutathione (GSH) level and glucose-6-phosphate dehydrogenase (G6PD) activity in gill and liver. There was increasing accumulation of the metals in the tissues with increasing concentrations of metals in the exposure medium and with increasing duration of exposure (except at the lower concentration of Zn). Concentration of metals in the tissues of fish exposed to the Zn + Cd combination were significantly lower than in fish exposed to the single metal. The highest metal accumulation was observed in the liver. Exposure to the heavy metals affected the antioxidant parameters in the tissues, with both GSH level and G6PD activity in the gill and liver being increased under Zn, Cd and Zn + Cd exposures, especially in their higher concentrations. These increases in the antioxidant responses were higher with the Cd alone, and in combination with Zn, than with Zn alone. Furthermore, GSH level and G6PD activity increased with increasing exposure period only for Cd alone, and in Cd combination with Zn. The results indicate that O. niloticus resisted oxidative stress induced by heavy metal exposure by antioxidant mechanisms. Copyright (C) 2008 John Wiley & Sons, Ltd.