The multiplication of red sea bream iridovirus (RSIV : KM99 from red sea bream) was investigated in the two groups of grouper Epinephelus malabaricus (average body weight, 7.7 g and 84.3 g) intraperitoneally inoculated with the virus at 28°C. Dead fish were observed from 8th day post-inoculation, and the cumulative mortality was 90% in fish of both sizes. Viral antigen-positive cells were detected with an indirect immunofluorescence test using a monoclonal antibody in the spleen and head kidney of the infected fish from 2nd day post-inoculation and in the liver and body kidney from 6th day post-inoculation. The number of positive cells in the spleen and head kidney was higher than that in the liver and body kidney. Transmission electron microscopy showed that the multiplication of the virus occurred in the enlarged cells in the fish at 4th day post-inoculation. In the dead fish, virus particles were found around the disrupted enlarged cells and small blood vessels. These findings suggest that the enlarged cells form primarily in the spleen and head kidney of the infected grouper as a result of viral multiplication and that the cells move to other organs via blood vessels and cause disruption by releasing progeny viruses.