This cohort descriptive study summarizes the epidemiological, clinical, and laboratory characteristics of the Rift Valley fever (RVF) epidemic that occurred in Saudi Arabia from 26 August 2000 through 22 September 2001. A total of 886 cases were reported. Of 834 reported cases for which laboratory results were available, 81.9% were laboratory confirmed, of which 51.1% were positive for only RVF immunoglobulin M, 35.7% were positive for only RVF antigen, and 13.2% were positive for both. The mean age (+/- standard deviation) was 46.9+/-19.4 years, and the ratio of male to female patients was 4:1. Clinical and laboratory features included fever (92.6% of patients), nausea (59.4%), vomiting (52.6%), abdominal pain (38.0%), diarrhea (22.1%), jaundice (18.1%), neurological manifestations (17.1%), hemorrhagic manifestations (7.1%), vision loss or scotomas (1.5%), elevated liver enzyme levels (98%), elevated lactate dehydrogenase level (60.2%), thrombocytopenia (38.4%), leukopenia (39.7%), renal impairment or failure (27.8%), elevated creatine kinase level (27.3%), and severe anemia (15.1%). The mortality rate was 13.9%. Bleeding, neurological manifestations, and jaundice were independently associated with a high mortality rate. Patients with leukopenia had significantly a lower mortality rate than did those with a normal or high leukocyte count (2.3% vs. 27.9%; odds ratio, 0.09; 95% confidence interval, 0.01-0.63).