Prophylactic and therapeutic efficacy of recombinant leukocyte A interferon (rIFN-αA) and Sendai virus-induced human leukocyte interferon (HuIFN-α) administered intramuscularly to Rift Valley fever virus (RVFV)-infected rhesus monkeys was studied. Clinical, virologic, immunologic, and hemostatic parameters were monitored. Five daily inoculations of 5 × 105 units of either interferon product per kilogram of body weight, initiated 24 hours before or 6 hours after RVFV infection, prevented or greatly suppressed viremia. No clinical signs of disease or laboratory evidence of impaired hemostasis was observed. Serum neutralizing antibody to RVFV was detected within 6 days of virus inoculation. Prophylactic administration of 5 × 104 or 5 × 103 units of rIFN-aA per kilogram also limited viremia, hepatocellular damage, and hemostatic derangement. Untreated, RVFVinfected, control monkeys developed high-titered viremia, clinical disease, and impaired hemostasis. These data suggest that rIFN-αA and HuIFN-α are effective in protecting RVFV-infected rhesus monkeys from viremia and hepatocellular damage and may be beneficial in human RVF infection.