An isolated epizootic of a highly fatal feline calicivirus (FCV) infection, manifested in its severest form by a systemic hemorrhagic-like fever, occurred over a 1-month period among six cats owned by two different employees and a client of a private veterinary practice. The infection may have started with an unowned shelter kitten that was hospitalized during this same period for a severe atypical upper respiratory infection. The causative agent was isolated from blood and nasal swabs from two cats; the electron microscopic appearance was typical for FCV and capsid gene sequencing showed it to be genetically similar to other less pathogenic field strains. An identical disease syndrome was recreated in laboratory cats through oral inoculation with tissue culture grown virus. During the course of transmission studies in experimental cats, the agent was inadvertently spread by caretakers to an adjoining room containing a group of four normal adult cats. One of the four older cats was found dead and a second was moribund within 48-72h in spite of symptomatic treatment; lesions in these animals were similar to those of the field cats but with the added feature of severe pancreatitis. The mortality in field cats, deliberately infected laboratory cats, and inadvertently infected laboratory cats ranged from 33-50%. This new isolate of calicivirus, named FCV-Ari, was neutralized at negligible to low titer by antiserum against the universal FCV-F9 vaccine strain. Cats orally immunized with FCV-F9, and then challenge-exposed shortly thereafter with FCV-Ari, developed a milder self-limiting form of disease, indicating partial protection. However, all of the field cats, including the three that died, had been previously immunized with parenteral FCV-F9 vaccine. FCV-Ari caused a disease that was reminiscent of Rabbit Hemorrhagic Disease, a highly fatal calicivirus infection of older rabbits.