SUMMARY Nine steers persistently infected with noncytopathic bovine viral diarrhea (bvd) virus were allotted into 3 groups (3 cattle/group). Cattle in group A were vaccinated with a modified-live bvd virus vaccine of porcine cell origin, cattle in group B with a modified-live bvd virus vaccine of bovine cell origin, and cattle in group C with a killed bvd virus vaccine of bovine cell origin. Detrimental effects due to vaccination were not seen. Six weeks after vaccination, the steers were challenge exposed with a cytopathic bvd virus. All steers developed mucosal disease after challenge exposure, produced antibodies that neutralized various isolates of bvd virus, and remained persistently infected until death. Steers given killed virus vaccine had a minimal neutralizing-antibody response and developed mucosal disease as quickly as reported for challenge-exposed, nonvaccinated, persistently infected cattle. Steers given modified-live virus vaccines had higher neutralizing-antibody response and longer intervals from challenge exposure to development of mucosal disease. The specificity of the neutralizing-antibody response differed between groups of vaccinated cattle.