FcγRIIB are low-affinity receptors for IgG whose intracytoplasmic domain contains an immunoreceptor tyrosine-based inhibition motif (ITIM). FcγRIIB inhibit cell activation triggered by receptors that signal via immunoreceptor tyrosine-based activation motifs. This inhibition requires ITIM tyrosyl phosphorylation and is correlated with the binding of SH2 domain-containing phosphatases that may mediate the inhibitory signal. In the present work, we investigated the mechanism of FcγRIIB phosphorylation and its consequences in mast cells. We demonstrate that the phosphorylation of FcγRIIB requires coaggregation with FcεRI and that, once phosphorylated, FcγRIIB selectively recruit the inositol polyphosphate 5 phosphatase SHIP, in vivo. In vitro, however, the phosphorylated FcγRIIB ITIM binds not only SHIP, but also the two protein tyrosine phosphatases, SHP-1 and SHP-2. We show that the coaggregation of FcγRIIB with FcεRI does not prevent FcεRI-mediated activation of lyn and syk. Both kinases can phosphorylate FcγRIIB in vitro. However, when coaggregated with FcεRI, FcγRIIB was in vivo phosphorylated in syk-deficient mast cells, but not in lyn-deficient mast cells. When FcεRI are coaggregated with FcγRIIB by immune complexes, FcεRI-associated lyn may thus phosphorylate FcγRIIB. By this mechanism, FcεRI initiate ITIM-dependent inhibition of intracellular propagation of their own signals.