The complex etiology of mucosal disease of cattle has been unravelled by experimental reproduction of the fatal syndrome, thereby validating Koch’s postulates. The causal virus, bovine virus diarrhea virus (BVDV), has two biotypes, noncytopathogenic and cytopathogenic; the former can infect the early bovine fetus, induce immunotolerance and a lifelong persistent viremia (pv), whereas the latter biotype can superinfect the pv cattle and induce mucosal disease. The cytopathogenic biotype appears able to originate de novo from the persisting virus by molecular rearrangement (e.g. template switching) and has been shown to arise in a case of spontaneous mucosal disease. The animal had been maintained in isolation for an extended perio