Cultured mast cells derived from murine bone marrow were investigated for the presence of specific interferon‐γ (IFN‐γ) receptors, and for the effects of IFN‐γ on mast cell proliferation. ¹²⁵I‐labeled recombinant IFN‐γ (¹²⁵I‐Mu‐rIFN‐γ) was shown to bind to high‐affinity receptors on these cells. Scatchard analysis of binding data indicated the presence of about 500 homogeneous binding sites per cell, with an apparent equilibrium dissociation constant of 3×10⁻¹⁰ M. The binding of ¹²⁵I‐Mu‐rIFN‐γ to mast cells was inhibited by unlabeled Mu‐rIFN‐γ but not by unlabeled Mu‐IFN‐α/β. Cross‐linking of ¹²⁵I‐Mu‐rIFN‐γ to mast cell membrane proteins using a cross‐linking agent yielded a predominant complex of 100 ± 10 kDa on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and autoradiography which IFN‐γ‐receptor complex. To assess the biological significance of these receptors, we studied the effects of Mu‐rIFN‐γ on mast cell proliferation, which was markedly inhibited in mast cell precursors but not in mature mast cells. These in vitro results are in agreement with the antiproliferative effect of IFN‐γ previously reported for other hematopoietic progenitors, and suggest that IFN‐γ could find its application in the treatment of human systemic mastocytosis.