Enteroviruses (EVs) are responsible for an array of clinical diseases affecting different systems of the organism. Many cases are asymptomatic; the most severe clinical syndromes caused by EVs are due to infection of the central nervous system and present as aseptic meningitis or encephalitis. We report here a large outbreak of enteroviral meningitis that spread in Marseilles, France, during the year 2000. The dominant strain of the outbreak was genetically identified as a human echovirus 30. The study was conducted prospectively from May to December 2000, with an investigative protocol recording epidemiologic, clinical, and laboratory data. A total of 250 patients with febrile neurologic manifestations were included between May 15 and December 30, 2000. A total of 195 cerebrospinal fluid (CSF) samples, 114 throat swabs, and 85 stool specimens were processed through viral culture and resulted in respectively 117 (60%), 61 (54%), and 58 (68%) cultures positive for EV; 69/106 (65%) CSF samples tested positive for the presence of EV RNA. None of the throat swab cultures but 5 of the stool cultures in control patients were positive. One hundred thirty-nine (55.6%) patients were considered confirmed cases because they had positive culture or reverse transcription polymerase chain reaction (RT-PCR) in CSF, and 38 (15.2%) patients were considered probable cases because they had a positive throat and/or stool culture and a negative (or not performed) procedure in CSF. The 177 confirmed and probable cases were not significantly different from the remaining 73 patients in terms of age distribution and epidemiologic, clinical, and biologic characteristics. The median age was 18.4 years (range, 15 d to 84 yr), and 92% of patients were younger than 40 years old. The male:female sex ratio was 1.8:1. We found no evidence of cases spread in nosocomial, household, or institutional settings, or limited community spread. All patients were immunocompetent except 4 adults. Meningoencephalitis represented 5.6% of cases. All but 3 of the 177 patients had a good outcome without sequelae. Two immunocompetent adults with meningoencephalitis had neurologic sequelae and an immunosuppressed adult had a fatal outcome. Upper respiratory symptoms were noted in 18.5% of patients, diarrhea in 11.5%, various types of rash in 4.5%, and myalgia in 3.8%. In CSF, white cell count was elevated in 90% of cases, with a percentage of neutrophils >50% in 55% of cases. Protein level was increased in 43% of cases. In blood, C-reactive protein was elevated in 67% of cases. Other blood parameters were unremarkable. Clinical and laboratory features did not differ from those related to other pathogens that caused meningitis and meningoencephalitis. Hence, unnecessary treatment for other infections is frequently instituted during EV infections. Virologic diagnosis is important to distinguish between EV and other treatable bacterial and viral diseases.