In this review I deal with antigen presentation and focus primarily on the antigen-presenting function of the macrophage. The two main topics consid ered here are:(a) handling of antigen by the macrophage and the general concept of" antigen processing"; and (b) the modulation of antigen-presenting cell (APC) function. In the latter section, I discuss APC other than the mac rophage. Because previous reviews (1, 2) have considered in detail the inter actions between the macrophage and the T cell, I emphasize more recent studies here. The overwhelming evidence at present supports the following statements:(a) helper T cells are not activated by direct interactions of their receptors with soluble antigen;(b) the clones of helper T cells are activated by their interaction with antigen presented by an APC that must bear the Class II glycoproteins of the Major Histocompatibility Gene Complex (MHC) of the species-the Ia antigens; and (c) under physiological conditions of immuni zation, the clones of T cells and APC share the same allelic form of their Class II molecules.