We studied early clinical features of the West Nile virus (WNV) infection. Case patients were Ohio residents who reported to the Ohio Department of Health from August 14 to December 31, 2002, with a positive serum or cerebrospinal fluid for anti-WNV IgM. Of 441 WNV cases, medical records of 224 (85.5%) hospitalized patients were available for review. Most frequent symptoms were fever at a temperature of 38.0 degrees C or higher (n = 155; 69.2%), headache (n = 114; 50.9%), and mental status changes (n = 113; 50.4%). At least one neurological symptom, one gastrointestinal symptom, and one respiratory symptom was present in 186 (83.0%), 119 (53.1%), and 46 (20.5%) patients, respectively. Using multivariate logistic regression and controlling for age, we found that the initial diagnosis of encephalitis (P = .001) or reporting abdominal pain (P < .001) was associated with death. Because initial symptoms of WNV infection are not specific, physicians should maintain a high index of suspicion during the epidemic season, particularly in elderly patients with compatible symptoms.