The present study is designed to examine the effect of zinc deficiency and possible role of zinc on morphine antinociception in mice. Therefore, mice were divided into four groups: 1) Zinc-deficient, 2) Pair-fed, 3) Control-morphine, and 4) Control-saline groups. Mice were fed during eight weeks of the study. At the end of this period 1.5 mg.Kg(-1) morphine was injected into mice except for the control-saline group and 20 min later the antinociceptive effect of morphine was evaluated by tail immersion test. In spite of morphine injection, the tail withdrawal latency of zinc-deficient mice was not different from control-saline (p > 0.05). The same parameter in pair-fed group was significantly different from control-saline (p < 0.05) and control-morphine groups. On the other hand, there was no difference between pair-fed and control-morphine groups (p > 0.05). In addition, plasma zinc levels of zinc-deficient mice were significantly lower than other groups (p < 0.05). Our results suggest that zinc deficiency may prevent the antinociceptive effects of morphine. Zinc may be necessary in physiologic range for morphine to exert antinociception activity.