On September 10, 2000, the Ministry of Health (MOH), Kingdom of Saudi Arabia, and subsequently the Ministry of Health of Yemen received reports of unexplained hemorrhagic fever in humans and associated animal deaths from the southwestern border of Saudi Arabia and Yemen. Signs and symptoms of ill persons included low grade fever, abdominal pain, vomiting, diarrhea, jaundice with liver and renal dysfunction often progressing to disseminated intravascular coagulation, hepatorenal syndrome, and death. On September 15, using ELISA (antigen detection and IgM), polymerase chain reaction, virus isolation, and immunohistochemistry, CDC confirmed the diagnosis of Rift Valley fever (RVF) in all four serum samples submitted from Saudi Arabia. This report summarizes the preliminary results of the collaborative epidemiologic investigation performed by the Saudi Arabian MOH, CDC, and the National Institute of Virology, South Africa, of the first confirmed occurrence of RVF outside Africa.