Abstract. Feline infectious peritonitis (FIP) is a fatal, coronavirus (CoV)-induced systemic disease in cats, characterized by granulomas in organs and granulomatous vasculitis. This study describes the morphologic features of granulomatous vasculitis in FIP as well as its development in the course of monocyte-associated feline CoV (FCoV) viremia in five naturally infected Domestic Shorthair cats with FIP. Monocyte-associated FCoV viremia was demonstrated by immunohistology, RNA in situ hybridization, and electron micropscopy. Granulomatous phlebitis at different stages of development was observed. Vasculitic processes ranged from attachment and emigration of FCoV-infected monocytes to vascular/perivascular granulomatous infiltrates with destruction of the vascular basal lamina. Monocytes as well as perivascular macrophages were activated because they were strongly positive for CD18 and expressed cytokines (tumor necrosis factor-␣ and interleukin-1) and matrix metalloproteinase-9. In addition, general activation of endothelial cells, represented by major histocompatibility complex II upregulation, was observed in all cases. These results confirm FIP as a monocyte-triggered systemic disease and demonstrate the central role of activated monocytes in FIP vasculitis.Key words: Cats; feline coronavirus; feline infectious peritonitis; granulomatous vasculitis; monocyte-associated viremia; phlebitis.Feline infectious peritonitis (FIP) is a well-known and widely distributed coronavirus (CoV)-induced systemic disease in cats, characterized by fibrinous to granulomatous serositis with protein-rich effusions in body cavities and granulomatous inflammatory lesions in several organs. 24,45 Not the most obvious finding, but one of its morphologic hallmarks is a granulomatous to necrotizing phlebitis and periphlebitis. 8,16,24,43 Up till now, the pathogenesis of FIP is largely undetermined.Feline CoV (FCoV) is transmitted via the fecal-oral route and primarily infects enterocytes. 28 Despite the generally high prevalence of FCoV infection among the cat population, especially in multicat facilities, FIP morbidity is low and rarely surpasses 5%. 1,7,28 FIP seems to develop in the individual infected animal when FCoV acquires virulence by deletions in open reading frames 3 and 7, coding for nonstructural proteins of unknown function, which occur as mutations primarily during replication in the infected host. 39 Most infected cats develop an FCoV viremia that can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) on isolated (and cultivated) monocytes regardless of the development of FIP. 7,15 FCoV-1 Present address: Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool, UK infected circulating monocytes are considered as responsible for viral dissemination within the host. 10,11,28,44 Furthermore, the demonstration of FCoV antigen within intravascular leukocytes and among cells in the lesions of vasculitis in a previous experimental study suggested that the inf...