Receptors for the third component of complement (C3) on cultured human monocytes (MO) bind ligand-coated particles but do not initiate phagocytosis. The function of these receptors, however, is altered dramatically after MO attach to surfaces coated with fibronectin (FN) or after MO are exposed to phorbol esters. FN and phorbol esters "activate" C3 receptors such that they promote vigorous phagocytosis. Here we show that activation of C3 receptors requires the continuous presence of FN or phorbol esters and is rapidly reversible when these stimuli are removed. Activation does not change the number or distribution of C3 receptors on the surface of MO. We conclude that the function of C3 receptors is regulated by reversible reactions that are initiated by ligation of a different class of receptors on the surface of the same cell.