Persistent versus transient infections: BVDV causes two types of infection in vivo. Infection of a seronegative animal with BVDV of either biotype leads to a transient (acute) infection that usually causes no or mild clinical symptoms. The virus will be eliminated by the humoral and cellular immune response that will protect the animal from further infections. In contrast, infection with ncp, but not cp, BVDV between the second and fourth month of gestation may lead to persistent infection of the fetus. Infection later in gestation may lead to abortion, malformation, or to the birth of normal, immunocompetent calves. PI calves are immunotolerant to the infecting BVDV strain. These animals are born antibody negative and shed large amounts of virus during their entire lifetime. If the persisting ncp virus mutates into a cp biotype or if the PI animal is superinfected with an antigenically related cp virus, the PI calf will succumb to the lethal mucosal disease. (A color version of this figure is available at www.vetres.org.)