The report is an overview of enterovirus epidemiology in Piemonte during a 5-year period from 2000 to 2004 with an investigative protocol recording epidemiologic, clinical, and laboratory data. A total of 1232 clinical cerebrospinal fluid (CSF) were collected from patients having clinical manifestations of aseptic meningitis (AAM) or encephalitis. Enterovirus detection was performed by isolation on cell culture (MRC5, BGM, Hep 2 e VERO) according to World Health Organization recommended protocols, and molecular methods based on reverse transcription (RT)-PCR. Isolates were identificated by indirect immunofluorescence staining with commercially available monoclonal antibodies and serotype identification was performed by seroneutralization (Lim and Benyesh-Melnick) of the cytopathic effect using pools of specific antisera. Twenty-six patients (2.1%), 15 males and 21 females, were found positive for Enterovirus with at least one of the test used.The average age was 23 (6-43).A total of 26 Non-Polio Enterovirus (NPEV) strains were isolated (11 Echovirus, 5 Coxsackievirus, 10 not identified); the dominant strain of the outbreak was identified as a human Echovirus 6 (4 cases) followed by Echo 31 (3), Coxsackie B5 (3), Echo 17 (2) Echo 9, 11, (1) and Coxsackie A16 (1). The yearly distribution of positive cases was homogeneous; a seasonal variation was noted with a predominance in summer-autumn; the higher transmission period starts in May and peaks in June-July; sporadic cases were also observed in winter and spring.