For the investigation of whether inflammatory cells were responsible for virus-induced airway hyperresponsiveness, tracheal spirals from healthy guinea pigs were incubated in organ baths with different numbers of bronchoalveolar cells obtained from guinea pigs 4 days after their inoculation with parainfluenza-3 (P-3) virus or control solution. Airway responsiveness was measured by performance of histamine concentration/response (C/R) curves on the tissues. Preparations incubated with 5 x 10(5) cells/ml obtained from guinea pigs treated with P-3 virus demonstrated a significant upward shift of the histamine C/R curve. The maximal contraction was increased by 26% as compared with the tissues incubated with the same number of cells from animals inoculated with control solution. When the number of cells was increased further to 5 x 10(6) cells/ml, no additional upward shift of the C/R curve was seen; the increase in maximal contraction was 24%. Tracheal spirals incubated with 5 x 10(4) cells/ml did not affect the histamine C/R curves. Addition of P-3 virus to the organ bath during the incubation period with the cells did not affect the histamine C/R curve either, irrespective of the inoculation solution or the number of bronchoalveolar cells used. The relative number of alveolar macrophages in bronchoalveolar lavage fluid decreased significantly from 86.3% +/- 2.6% in the control group to 71.8% +/- 3.3% in the P-3 virus group as a consequence of a significant increase in the percentage of monocytes, lymphocytes, and eosinophils. These results suggest that bronchoalveolar cells are causally involved in the virus-induced airway hyperresponsiveness.