The mechanism of C5a des Arg-induced airway hyper-responsiveness in rabbits was investigated. Airway smooth muscle from rabbits which had been pretreated in vivo, was studied in vitro. Tracheal rings, segmental bronchial rings, subsegmental bronchial spirals and lung parenchymal strips were all prepared from each rabbit lung. Although C5a des Arg produces hyper-responsiveness to histamine in vivo, which is inhibited by indomethacin, the airway smooth muscle responses in vitro from control, C5a des Arg and C5a des Arg plus indomethacin pretreated rabbits did not differ. The neutrophil counts in the tracheal and subsegmental bronchial specimens were increased in the C5a des Arg-treated group. Indomethacin significantly (P less than 0.05) inhibited the neutrophil influx in the subsegmental bronchi. It is concluded that intrinsic smooth muscle function is unaltered following C5a des Arg-induced hyper-responsiveness in vivo.