The effusive form of feline infectious peritonitis (FIP) was reproduced by injecting 12- to 16-week-old kittens intraperitoneally with a cell-free inoculum derived from the tissues of infected cats. The kittens used for the study were either positive for FIP virus-reacting antibodies before inoculation or they were seronegative. Seropositive kittens were obtained from a cattery where the natural infection was enzootic, and seronegative kittens were obtained from a specific-pathogen-free cattery. Only about half the kittens that were seronegative before inoculation developed disease or serum antibodies to the tissue-derived virus. Seronegative kittens that developed disease showed no signs of illness until 8 to 10 days after inoculation, and they lived for 7 to 14 days after clinical signs appeared. The onset of clinical disease coincided with the appearance of serum antibodies. In contrast, all of the seropositive kittens became ill within 36 to 48 hours after inoculation, and died within 5 to 7 days. If seronegative kittens were treated with immune serum or immunoglobulin (Ig)G, they developed disease with the same frequency, acuteness, and severity as seropositive kittens. Foci of hepatitis and serositis in seropositive kittens contained viral antigen, IgG bound to antigen, and complement. Serum complement activity also decreased several days before death in seropositive kittens inoculated with tissue-derived FIP virus. The temporal relationship of clinical disease and the appearance of serum antibodies, the more acute and severe nature of the disease produced in seropositive kittens, and the presence of antibody and complement in the lesions indicated that effusive FIP is immunologically mediated.