The purpose of this study was to investigate for the change in cough reflex sensitivity (CRS) caused by parainfluenza virus type 3 (PIV3) infection. Guinea pigs were randomized into a vehicle control, an asthma control, or 1 of 4 PIV3-inoculated groups (referred to as postinfection day [PID] 6, 12, 28, and 42 groups). Evidence of viral protein and nucleic acid within the lung confirmed successful PIV3 infection. Plethysmography was used to assess CRS and airway reaction and airway inflammation was assessed via bronchoalveolar lavage fluid cytology and lung histopathology. Compared with the vehicle control group, CRS was significantly increased in all PID groups (P <.05) in concert with an obvious airway hyperresponsiveness in the PID 6 group. Though a small increase in CRS in the asthma control group was noted, it was not significant compared to the vehicle control group. Total cell counts from the bronchoalveolar lavage fluid of all PIV3-inoculated groups increased markedly and the number of lymphocytes was significantly increased in the PID 6 and PID 12 groups. The lung pathology of PIV3-inoculated animals showed airway inflammation without pneumonia in the acute infectious phase. The temporal and spatial variation of CRS may be the essential mechanism of cough caused by PIV3.