We have used human-rodent somatic cell hybrids to investigate the regional localization of the IFN-gamma R gene on human chromosome 6 and studied functional and antigenic characteristics of the expressed IFN-gamma R by Scatchard analyses of 125I-IFN-gamma binding and binding of an anti-receptor mAb (A6C5). The data obtained revealed coordinate expression of IFN-gamma- and A6C5-binding capacity as well as competition in binding to chromosome 6-positive hybrids and normal cells, indicating that the A6C5-defined protein is by itself capable of high affinity IFN-gamma binding and, thus, is likely to constitute the major IFN-gamma R protein of distinct cell types. The receptor gene could be allocated to region 6q16 to 6q22, which also contains the c-ros oncogene. Genetic linkage of the IFN-gamma R gene to an oncogene located in a region of non-random chromosomal aberrations may have a causal relationship to the deregulated IFN-gamma R expression in several malignancies.