BACKGROUND West Nile fever (WNF) is a mosquito-borne flavivirus infection endemic in Africa and Asia. In 1996, the first major WNF epidemic in Europe occurred in Romania, with a high rate of neurological infections. We investigated the epidemic to characterise transmission patterns in this novel setting and to determine its origin. METHODS Hospital-based surveillance identified patients admitted with acute aseptic meningitis and encephalitis in 40 Romanian districts, including Bucharest. Infection was confirmed with IgM capture and indirect IgG ELISAs. In October, 1996, we surveyed outpatients in Bucharest and seven other districts to estimate seroprevalence and to detect infected patients not admitted to hospital. We also measured the rates of infection and seropositivity in mosquitoes and birds, respectively. RESULTS Between July 15 and Oct 12, we identified 393 patients with serologically confirmed or probable WNF infection, of whom 352 had acute central-nervous-system infections. 17 patients older than 50 years died. Fatality/case ratio and disease incidence increased with age. The outbreak was confined to 14 districts in the lower Danube valley and Bucharest (attack rate 12.4/100000 people) with a seroprevalence of 4.1%. The number of mild cases could not be estimated. WN virus was recovered from Culex pipiens mosquitoes, the most likely vector, and antibodies to WN virus were found in 41% of domestic fowl. CONCLUSIONS The epidemic in Bucharest reflected increased regional WNF transmission in 1996. Epidemics of Cx pipiens-borne WNF could occur in other European cities with conditions conducive to transmission.