CD4(+) T lymphocytes play an essential role in the induction and regulation of the immune response. The two subpopulations, Th1 and Th2, are also able to activate various immune functions via their capacity to synthesize various cytokine patterns. CD4(+) T lymphocytes are activated by interaction of the T receptor with a bimolecular complex composed of a peptide derived from processing of the antigen and a major histocompatibility complex class II molecule. Only a limited number of cells are able to activate CD4(+) T lymphocytes. Monocytes/macrophages, dentritic cells and B lymphocytes are usually responsible for presentation of the antigen to CD4(+) T lymphocytes. The capacity of phagocytosis, B7 molecules expression and the nature of the cytokine produced differ between these various cell types. This may play an essential role in the preferential activation of one or other of the Th1 and Th2 subpopulations. Particulate antigens were prepared by covalent binding to synthetic microspheres in order to orient CD4(+) T lymphocyte responses towards Th1 polarisation. These particles were presented to T lymphocytes by macrophages, but not by B lymphocytes. When injected in the presence of poly (I)-(C) or IL-12, these particulate antigens preferentially activated a Th1 type response.