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Background: This study hypothesizes that predicted polymorphism of the interferon-gamma receptor 1 gene may play an important role in infection after trauma as supported by microsatellite analysis., Methods: DNA was extracted from the peripheral leukocytes of 38 trauma patients with Injury Severity Scores greater than 16. D6S471, a microsatellite marker on chromosome 6 near interferon-gamma receptor 1, was amplified with polymerase chain reaction, and genotypes were determined., Results: The mean Injury Severity Score was 32, and 63% of patients (24 of 38) developed major infection. Three alleles and 5 genotypes were identified for D6S471. Twenty-six percent of patients (10 of 38) had genotype AA, all of whom developed major infection (P =.004). Genotype BB accounted for 57% of the uninfected population (8 of 14) but only 21% of the infected group (P =.028). Allele A had a frequency of 33%, of which 22 alleles (88%) were found in infected patients (P =.001). In addition, allele B accounted for 61% of the uninfected group (17 of 28) but only 23% (11 of 48) of the infected group (P =.001). Allele C demonstrated no correlation., Conclusions: Microsatellite polymorphism correlates strongly with infection. These findings portend polymorphism in the receptor itself and thereby represent a genetic basis for the development of infection. We suggest this identifies a high-risk group who could benefit from more specific therapy that may have the potential to overcome this receptor insufficiency.