The T cell-mediated acquired immune response to infection with Mycobacterium tuberculosis, both in humans and in experimental models in the mouse, is a complex event believed to involve a variety of T cell subsets that manifest themselves in numerous functions, including protection, delayed-type hypersensitivity, cytolysis, and the establishment of a state of memory immunity. These functions in turn involve the secretion of an array of cytokines, several of which direct cells of the monocyte/macrophage axis to contain and destroy the invading bacilli. This article reviews the development of these ideas, both from clinical experience and from basic research in animal models. In addition, the newly emerging hypothesis that the secreted or export proteins of M. tuberculosis are the key protective antigens leading to the initial expression of acquired specific resistance to this organism is examined.