IMMUNE complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc receptors (FcRs) such as Fc epsilon RI or Fc gamma RIII (ref, 1). On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc receptors, a consequence of coligation of the B-cell antigen receptor or Fc epsilon RI, respectively, and the inhibitory receptor Fc gamma RIIB. Here we show that inhibitory signalling by Fc gamma RIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of Fc gamma RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P-3 and inositol(1,3,4,5) P-4, suggests a mechanism by which Fc gamma RIIB can inhibit calcium influx and downstream responses triggered by immune receptors.