The effects of zinc depletion and repletion on spleen natural killer (NK) cell activity in aged mice were studied. Sixty 24-month-old male Balb/c mice were divided equally into three groups according to their weight: group I were fed the zinc-deficient diet (1.3 μg/g Zn). Group II were fed the zinc-supplemented diet (58 μg/g Zn), but their intake was restricted to the average daily amount consumed by the zinc-deficient group and group 111 were fed the zinc-supplemented diet (58 μg/g Zn) ad libitum. After 4 weeks, 10 mice were taken out from each group. The determinations of NK cell activity and plasma zinc level were performed in aged mice. Then, the other 10 mice in each group were all fed the zinc-supplemented diet. After another 4 weeks, they were also killed and used for the measurements of NK cell activity and plasma zinc level. The results showed that the level of plasma zinc and spleen NK cell activity were both significantly lower in zinc-deficient mice than in the restricted mice and in the ad libitum controls (P<0.05). There was no statistical difference in plasma zinc level and NK cell activity between the restricted mice and the ad libitum controls (P>0.05). Supplementation of zinc for 4 weeks enabled a satisfactory recovery of all the indices in the zinc-deficient mice. The data suggest that zinc deficiency significantly impairs the spleen NK cell activity in aged mice, which can be satisfactorily recovered by an adequate zinc supplementation.