The aim of this work was to study the interstitial aggregates of immune cells observed in pulmonary parenchyma of calves preinfected with bovine viral diarrhea virus and challenged later with bovine herpesvirus 1. In addition, the intent of this research was to clarify the role of bovine viral diarrhea virus in local cell-mediated immunity and potentially in predisposing animals to bovine respiratory disease complex. Twelve Friesian calves, aged 8 to 9 months, were inoculated with noncytopathic bovine viral diarrhea virus genotype 1. Ten were subsequently challenged with bovine herpesvirus 1 and euthanized at 1, 2, 4, 7, or 14 days postinoculation. The other 2 calves were euthanized prior to the second inoculation. Another cohort of 10 calves was inoculated only with bovine herpesvirus 1 and then were euthanized at the same time points. Two calves were not inoculated with any agent and were used as negative controls. Pulmonary lesions were evaluated in all animals, while quantitative and biosynthetic changes in immune cells were concurrently examined immunohistochemically to compare coinfected calves and calves challenged only with bovine herpesvirus 1. Calves preinfected with bovine viral diarrhea virus demonstrated moderate respiratory clinical signs and histopathologic evidence of interstitial pneumonia with aggregates of mononuclear cells, which predominated at 4 days postinoculation. Furthermore, this group of animals was noted to have a suppression of interleukin-10 and associated alterations in the Th1-driven cytokine response in the lungs, as well as inhibition of the response of CD8þ and CD4þ T lymphocytes against bovine herpesvirus 1. These findings suggest that bovine viral diarrhea virus preinfection could affect the regulation of the immune response as modulated by regulatory T cells, as well as impair local cell-mediated immunity to secondary respiratory pathogens.Keywords bovine viral diarrhea virus, bovine herpesvirus type 1, lung, immune response, lymphocytes, immunohistochemistry Bovine viral diarrhea virus (BVDV) is an important pestiviral pathogen of cattle, causing considerable economic losses for the livestock industry. 25 The biology of BVDV is highly complex, depending on a variety of factors such as the viral genotype and biotype causing the infection, the immune status and age of the affected animals, and the gestational stage of cows in case of infection during pregnancy. 7,29,33,44 This leads to a broad spectrum of clinical manifestations and lesions, which are classified according to the type of BVDV infection-namely, acute infection, persistent infection, and mucosal disease. During acute infections, the pestivirus can induce severe reproductive, gastrointestinal, and respiratory disease in cattle. 21,38,49