Early events in an immune response stimulate the production of cytokines that direct the subsequent development of T-helper (Th) subsets with discrete patterns of cytokine production. These events are dictated by the type of antigen/microorganism administered to a host, as well as dose and route of immunization. Bacterial stimuli activate macrophages of the innate immune response to produce IL-12 and drive Th1 development and cell-mediated immunity. Conversely, production of IL-4 early in an immune response favors a Th2 or allergic/humoral immune response. The ability of IL-4 and IL-10 to inhibit Th1 development and effector function, as well as the requirement of committed Th1 cells for co-stimulators to induce maximal IFN-gamma production, suggests that cell-mediated immunity is under strict control, probably to achieve immunity with minimum immunopathology.