Individuals with inherited disorders of interferon-γ (IFN-& gamma)-mediated immunity appear to be specifically vulnerable to mycobacterial infections. The severity of clinical features of affected individuals differs between cases. Some patients die of mycobacterial infection in early childhood, whereas others have long asymptomatic periods in childhood and as adults. This rare syndrome also shows high allelic and non-allelic genetic heterogeneity. Mutations in IL12B, encoding the interleukin (IL)-12 p40 subunit, and in IL12RB1, encoding the β1 chain of the IL-12 receptor, result in impaired IFN-γ production. Mutations in IFNGR1 and IFNGR2, encoding the two IFN-γ receptor chains, and mutations in STAT1, encoding an essential signaling component, result in impaired cellular responses to IFN-γ. Different types of mutation define two types of complete and two types of partial IFN-γR1 deficiency. Complete and partial IFN-γR2 deficiency have also been described. We herein compare the genotypes, cellular phenotypes, and clinical phenotypes of healthy individuals and patients with the seven known genetic disorders impairing cellular responses to IFN-γ. Patients with defective IFN-γ production were not considered in this study. The mutations and clinical features of patients with IFNγR1, IFNγR2, and STAT-1 deficiency are reviewed. Selected cell lines from each of the eight groups were tested for their response to IFN-γ. We find that individuals may be classified into four broad groups based on genotype, cellular phenotype, and clinical phenotype (normal individuals and patients with...