The IgE-FcεRI network plays a central role in allergic inflammation. IgE levels control cell surface levels of FcεRI and, in turn, FcεRI levels modulate the intensity of effector responses. Treatment of allergic patients with anti-IgE Abs has been shown to induce a decrease in FcεRI expression on basophils and a decrease in Ag-triggered histamine release. However, the mechanisms underlying IgE-mediated regulation of FcεRI expression remain unclear. Here, we designed an in vitro model system to establish the minimal cellular requirements for regulation of FcεRI by IgE. Using this system, we demonstrate that transcriptional regulation, hemopoietic-specific factors, and signaling are not required for IgE-mediated increases in FcεRI expression. IgE binding to the α-chain is the minimal requirement for the induction of FcεRI up-regulation. The rate of up-regulation is independent of the baseline level of expression. The mechanism of this up-regulation is the result of a combination of three factors: 1) stabilization of the receptor at the cell surface, which prevents receptor internalization and degradation; 2) use of a preformed pool of receptor comprising recycled and recently synthesized receptors; and 3) continued basal level of protein synthesis. It is possible that in vivo additional factors contribute to modulate the basic regulatory mechanism described here.