Coinfection with two or more pathogens is a common occurrence in respiratory diseases of most species. The manner in which multiple pathogens interact is not always straightforward, however. Bordetella bronchiseptica and porcine respiratory coronavirus (PRCV) are respiratory pathogens of pigs whose relatives, B. pertussis and the SARS virus, cause respiratory disease in humans. In an initial experiment, the effect of coinfection of PRCV and B. bronchiseptica was examined in thirty, 4-week-old pigs (10 pigs/group) that were infected with either PRCV or B. bronchiseptica, or both PRCV and B. bronchiseptica. An additional 10 pigs served as sham infected controls. Five pigs from each group were euthanized at 4 and 10 days post-infection. Gross and histopathological lung lesions were more severe in the coinfected group as compared to the groups infected with B. bronchiseptica or PRCV alone. In order to investigate the potential role of proinflammatory cytokines in disease severity after coinfection, a second experiment was performed to examine cytokine transcription in alveolar macrophages from single and dually infected pigs. A total of 48 pigs were divided equally into groups as above, but 4 pigs from each group were euthanized at 1, 4 and 10 days post-infection. Coinfected pigs showed a greater and more sustained transcription of proinflammatory cytokines, especially IL-6 and MCP-1, than pigs infected with either PRCV or B. bronchiseptica alone. Thus, there appears to be a synergistic effect between PRCV and B. bronchiseptica with regards to proinflammatory cytokine transcription that may partially explain the increased severity of pneumonia in coinfected pigs.