Summary A noncytopathic bovine viral diarrhea virus (bvdv), bvdv-890, isolated from a yearling heifer that died with extensive internal hemorrhages, was compared for virulence in calves with noncytopathic bvdv-TGAN, isolated from an apparently healthy persistently infected calf. After challenge exposure with bvdv-890, nonimmune calves (n = 7) developed fever > 40 C, diarrhea, leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Most calves (n = 6) died or were euthanatized by 19 days after challenge exposure. Challenge exposure with bvdv-890 did not induce disease in 2 calves that had congenital persistent infection with bvdv or in 3 calves that had neutralizing antibody titer > 4 against bvdv-890. After challenge exposure with bvdv-TGAN, nonimmune calves (n = 7) developed fever > 40 C and, rarely, diarrhea or lymphopenia. All of those calves survived challenge exposure. The average maximal titer of bvdv-890 isolated from serum was 1,000 times that of bvdv-TGAN. In calves infected with bvdv-890, the average maximal percentages of lymphocytes and platelets associated with virus were greater than those found in calves infected with bvdv-TGAN. Additional findings of epidemiologic significance were prolonged shedding of virus and delayed production of viral-neutralizing antibody in 1 calf challenge-exposed with bvdv-890. Also, after production of neutralizing antibody, mutant virus that was refractory to neutralization was isolated from calves challenge-exposed with bvdv-TGAN.