Prophylactic treatment of rhesus macaques with 10(4)-10(6) U/kg of recombinant human interferon-gamma (rHuIFN-gamma) modulated Rift Valley fever (RVF) virus infection. IFN was given intramuscularly at 24 h prior to infection and daily thereafter for a total of five doses. After infection, treated monkeys showed no evidence of clinical disease; some had no detectable viremia; when viremia was observed, peak virus titers were decreased compared to control infected monkeys; and only minor and transient perturbations in hematologic and clinical chemistry values were seen. Untreated infected control monkeys developed high-titered viremia, mild to severe clinical disease, and moderate to severe changes in hemostatic parameters and clinical laboratory measurements. No evidence of synergism was noted when RVF virus-infected monkeys were treated prophylactically with combined low doses of rHuIFN-gamma and rHuIFN-alpha A.