Cell-mediated immunity is defined as a beneficial host response characterized by an expanded population of specific T cells, which, in the presence of antigens, produce cytokines locally. The activation and recruitment of cells into an area of inflammation is a crucial step in the development of DTH responses. DTH is immunologically a process similar to cell-mediated immunity, involving T cells and cytokines. CD4 T helper (Th) 1 cells, differentiated from naive Th cells by IL-12 and IL-18 produced from macrophages, play a regulatory role in the expression of DTH and activation of macrophages via interferon γ generated by Th1 and natural killer cells. Macrophages accumulate at the site of DTH and become activated through the CD4 Th1 cell-cytokine-macrophage axis. However, DTH leads to pathologic responses, such as granulomatous inflammation, calcification, caseation necrosis, and cavity formation. Granulomas usually form as a result of the persistence of a nondegradable product or as the result of DTH responses. DTH is also required for host defense against etiologic agents, such as Mycobacterium tuberculosis. The expression of cell-mediated immunity/DTH is a double-edged sword that may contribute to both clearance of the etiologic agent and tissue damage. Microsc. Res. Tech. 53:241–245, 2001. © 2001 Wiley-Liss, Inc.