Evidence is accumulating to suggest the existence of polarized human T-cell responses, reminiscent of T_H1 and T_H2 subsets described for mouse T cells. Human T_H1 cells preferentially develop during infections by intracellular bacteria and trigger phagocyte-mediated host defense, whereas T_H2 cells, which predominate during helminthic infestations and in response to common environmental allergens, are responsible for phagocyte-independent host response. Human T_H1 and T_H2 cells exhibit not only different functional properties but probably also distinct surface markers; T_H2, but not T_H1, clones express membrane CD30 and release the soluble form of CD30, a member of the TNF receptor superfamily. The cytokine profile of “natural immunity” evoked by different offending agents in the context of different host genetic backgrounds appears to be the most critical factor in determining the phenotype of the subsequent specific response. IL-12 and IFN-α and γ produced by macrophages and NK cells favor the development of T_H1 cells, whereas the early production of IL-4 by a stillunidentified cell type favors the development of T_H2 cells. Clearly, polarized human T_H1 and T_H2 responses not only play different roles in protection, they can also promote different immunopathological reactions. Strong and persistent T_H1 responses seen to be involved in organ-specific autoimmunity, contact dermatitis, and some chronic inflammatory disorders of unknown etiology. In contrast, polarized T_H2 responses favor a reduced protection against the majority of infectious agents (including HIV) and, in genetically predisposed hosts, are responsible for triggering of allergic atopic disorders.