The efficacy of intranasal vaccination in preventing or limiting disease of the lower respiratory tract induced by parainfluenza 3 (P13) virus was evaluated under experimental conditions, using a commercially available live vaccine containing a temperature-sensitive strain of P13 virus. In a preliminary study four colostrum-deprived calves were vaccinated intranasally at one week and again at two months of age, and two similar calves were given an intranasal placebo. After the second vaccination serum antibodies to P13 virus were detected in all four vaccinated calves, but not in the control animals. Seventeen days after the second vaccination all six calves were challenged with virulent P13 virus, and they were killed six days later. The clinical scores and the extent of pulmonary consolidation were reduced in the vaccinated animals; P13 virus was detected in the upper and lower respiratory tract of the control calves but in none of the vaccinated calves. In a larger scale study with 14 colostrum-fed calves, seven were vaccinated at one week and again at five weeks of age, and seven were given an intranasal placebo. Two weeks after the second vaccination all 14 calves were challenged with virulent P13 virus. The clinical scores and lung consolidation were significantly reduced in the vaccinated calves in comparison with the controls. Six days after infection, 10 of the 14 calves were killed; P13 virus was detectable in the nasal secretions of all seven control calves but in only one of the vaccinated animals, and P13 viral antigen was detected in the lungs of the control calves but not in those of the vaccinated animals. One of the vaccinated calves had developed a severe clinical response after the challenge, but it had only minor lung consolidation when killed.