OBJECTIVE: Sandfly fever phleboviruses are endemic in Mediterranean countries. We report a febrile phlebovirus case in a Greek patient who presented signs of neuroinvasive infection.METHODS: In summer 2010, a 20-year-old male was admitted to hospital with fever and lethargy; he was a resident of central Macedonia, northern Greece, where a large outbreak of West Nile virus (WNV) infections occurred at that time. Since there was no laboratory evidence of WNV infection, the patient's serum and cerebrospinal fluid were tested for a probable phlebovirus infection.RESULTS: High titers of IgM and IgG antibodies against Toscana virus were detected in serum and cerebrospinal fluid, while the titers against sandfly fever Naples virus were lower; no reactivity was detected against sandfly Sicilian and Cyprus viruses. Since neutralization assays were not performed and PCR resulted in being negative, it was concluded that the causative agent was a phlebovirus of the sandfly fever Naples serocomplex.CONCLUSION: The present case confirms results from previous seroprevalence studies showing that phleboviruses of the sandfly fever Naples serocomplex are present in Greece and provides evidence that they cause febrile neuroinvasive disease in humans, prompting for inclusion of phleboviral infections in the differential diagnosis of acute febrile cases during the time when sandflies are active.