Administration of acetylsalicylic acid or mefenamic acid during experimental infection of rabbits with a rabbit-adapted strain of rinderpest virus did not prevent initiation of the febrile response but significantly reduced the duration of fever. Suppression of fever had a markedly deleterious effect on the course of infection, resulting in an increased content of infectious virus in the mesenteric lymph nodes, increased mortality, and retarded recovery in animals that survived the infection. Histological lesions were mainly lymphocytic depletion in lymphoid organs and lymphoid necrosis in both rabbits treated with antipyretics and those left untreated, but damage was more pronounced in the former than in the latter. More viral antigen was detected by immunofluorescence in lymphoid organs of drug-treated rabbits than in those of untreated rabbits. Antipyretic treatment resulted in higher serum interferon levels in the early phase of infection and an increased antibody response in animals that survived the infection.