Brown Norway (BN) rats are more susceptible than Fischer 344 (F344) rats to parainfluenza virus-induced lung injury and to bronchiolar mast cell increases that are associated with persistent airway hyperresponsiveness. In this study, pulmonary viral replication as well as immune, inflammatory, and airway mast cell responses to Sendai virus infection were compared between neonatal BN and F344 rats. BN rats supported prolonged viral replication, and viral titers in BN rats were 5-fold higher (p < .05) than in F344 rats at 7 days after inoculation. F344 rats had 18-fold higher (p < .06) numbers of lymphocytes in bronchoalveolar lavage fluid at 7 days after inoculation than did BN rats. Persisting bronchiolar aggregates of lymphocytes, plasma cells, and macrophages were more common, and increases in bronchiolar mast cells were greater in BN rats than in F344 rats. No strain differences were detected in bronchiolar intramural infiltrates of CD4 + or CD8 + cells. The greater susceptibility of BN rats to virus-induced increases in bronchiolar mast cells and airway responsiveness may be the result of their less efficient viral clearance mechanisms and more persistent bronchiole-centered inflammatory response.