The human interferon (IFN) gamma receptor cDNA has been stably expressed in human/mouse somatic cell hybrids, which differ in their content of human chromosome 21. Despite high affinity IFN gamma binding-capacity of all receptor transfectants, biological responsiveness to IFN gamma, as determined by enhancement of mouse-MHC class I gene expression, required the presence of chromosome 21. These data suggest complementation of at least two functionally distinct components in order to create a biologically active IFN gamma receptor.