We previously demonstrated that clenbuterol suppressed bronchial hyperresponsiveness in acute bronchitic models. However the effect of clenbuterol on the cough reflex, the main symptom of acute bronchitis, is not clear. The present study was thus undertaken to investigate the influence of clenbuterol on the cough reflex. Oral administration of clenbuterol (3 and 10 micrograms/kg) to guinea pigs markedly inhibited the increase in the respiratory resistance in response to 5-HT in a dose-dependent manner. At doses of 10 micrograms/kg and above, clenbuterol significantly inhibited the cough reflex induced by citric acid in guinea pigs. These doses are comparable with those causing broncho-dilation as described above, suggesting that the suppressive effect of clenbuterol on the cough reflex in guinea pigs may result from mainly its broncho-dilative action via stimulation of beta-2 adrenoceptors in airway smooth muscles however, other mechanisms cannot be ruled out. These results indicate that this agent may be useful for treatment of cough, the main symptom of acute bronchitis.