A large body of evidence has accumulated suggesting the existence of human TH1 and TH2 subsets, reminiscent of those described for mouse T cells. Human TH1 cells develop in response to intracellular bacteria and viruses, do not provide help for IgE synthesis and are cytolytic. Human TH2 cells develop in response to allergens and helminth components, provide help for IgM, IgG, IgA, and IgE synthesis and lack cytolytic potential. The cytokine profile of 'natural' immunity (high IFN-gamma and no IL-4 production) evoked by intracellular bacteria and viruses that activate both macrophages and NK cells, probably determines the phenotype of the subsequent specific TH1 response. Absence or low concentration of IFN-gamma and early production of IL-4 by non-T cells or by T cells themselves, that occur in response to allergens and helminth components, probably favor the development of TH2 cells. TH1 and TH2 cells play different roles not only in protection against exogenous offending agents, but also in immunopathology. TH1 cells are involved in contact dermatitis, organ-specific autoimmunity and allograft rejection. TH2 cells are responsible for the initiation of the allergic cascade.