This report describes a nosocomial outbreak of feline calicivirus (FCV) associated virulent systemic disease (VSD) in a French veterinary teaching hospital in 2005. The outbreak started in March and resolved within 1 month. Signs, clinical course, clinicopathological findings and lesions were typical of FCV-induced VSD. FCV infection was confirmed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Among the eight infected cats, two had to be euthanased, three died, and three recovered after medical treatment. Virus could not be confined inside the animal hospital and on two occasions, students' own cats became infected. Subsequent genetic sequencing studies confirmed that the eight cats were infected with the same strain of virus, and that it was distinct from those involved in the US and UK outbreaks of VSD. Virulence and viral excretion patterns of the isolated strain were further characterised by experimental infection.