Murine monoclonal antibodies (mAbs) are described that recognize the extracellular human interferon γ receptor α-chain (IFNγR) and inhibit the binding to it of interferon γ. The inhibitory activities (IC₅₀s) of these mAbs, quantified by radioimmunoassay using native receptor on human Raji cells, lie in the range 0.5–24 nM, whereas their relative affinities for the immobilised recombinant extracellular receptor, determined using surface plasmon resonance technology, are in the range 0.6–40.9 nM. Nine mAbs derived from one immunization, were shown by variable region cDNA sequencing to be clonally related, with mAb A6 from this group showing the highest affinity for the receptor. Another two mAbs, γR38 and γR99, derived from a separate immunization, are clonally unrelated to each other and to those in the A6 family. From the V-region sequences, the L-chains of mAbs A6, γR38 and γR99 were shown to belong to the V_κ34C, V_κ34C and V_κ1 families, whereas the H-chains belong to the 3069, J606 and J558 families, respectively. The mAbs A6 and γR38 recognize overlapping epitopes on the N-terminal Ig-like domain of the IFNγR, whereas the γR99 epitope is located largely in the membrane proximal Ig-like domain. Sequence comparisons with Ig structures solved by X-ray diffraction allowed deductions concerning likely CDR canonical conformations. These studies provide essential information for crystallographic and mutagenesis experiments aimed at understanding the molecular basis of the interactions of these mAbs with the extracellular IFNγR.