Metallothionein (MT) is a low molecular weight protein, rich in cystein residues, and induced by stimulation with several stresses such as heavy metals, chemical agents, oxygen radicals and irradiation. It is involved in metal metabolism, detoxification and radical scavenging and also participates in immune responses. In this communication, to study the role of MT in immune responses, we analyzed immune functions, especially macrophage functions in MT-knock out (MT-KO) mice in vitro. When compared with wild type counterpart (MT-WT) mice, macrophages from MT-KO mice showed a defect of phagocytic and antigen-presenting activity. Cytokine productions such as IL-1alpha, IL-6, IL-10 and IL-12 were reduced in macrophages from MT-KO mice. Furthermore, the expressions of CD80, CD86 and MHC class II molecules were also reduced in macrophages from MT-KO mice. No obvious dysfunction was observed in T cells and B cells. These results suggest that MT plays an important role in the regulation of immune responses, especially macrophage functions.