AbstractWe determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9–12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2‐CPI2, n = 7). We compared their acute responses to puppies infected with CPI2 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12–14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2‐CPI2 group, CPI2 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CPI2 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2‐CPI2 group. Airway histamine responsiveness in the CAV2‐CPI2 group increased during infection with CPI2 and was similar to that observed with CAV2 alone. In contrast, infection with CPI2 alone produced a small, but non‐significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2‐CPI2 group in comparison to CPI2 or CAV2 alone. However, the length of clinical illness was extended in the CAV2‐CPI2 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI. Pediatr Pulmonol 1991; 10:236–243.