1. In this study, the effects of lead acetate on two types of pain (nociception and inflammation) induced by formalin and its interactions with opioid system and morphine-induced analgesia were examined. Male albino mice weighing 22-27 g were used in the experiments. 2. To study nociception, the formalin test was selected. Morphine was administered subcutaneously 30 min before formalin injection. Lead acetate treatment was administered 90 min before any injection. Comparisons between groups were made by analysis of variance and then by Newman-Keuls test. Differences with P < or = 0.05 was considered statistically significant. 3. Different doses of morphine induced antinociception in both phases of the formalin test. Lead acetate induced non-dose-dependent nociception in the early phase and dose-dependent analgesia in the late phase. 4. Pretreatment with lead acetate antagonized the effect of morphine in the early phase. In the other hand, the effect of lead acetate in the early phase was reduced by morphine and its effect eliminated in the late phase. 5. It is concluded that lead can modulate pain response and interact with morphine-induced antinociception. Additional research to find the mechanisms of these effects are suggested.