In this study we investigated whether openers of potassium channels, K+ATP--pinacidil and BK+Ca--NS1619, modulate cough reflex and airway smooth muscle (ASM) reactivity in in vivo and in vitro conditions in guinea pigs. The cough reflex was induced by 0.3 M citric acid aerosol given for 3 min during which time a total number of coughs was counted. ASM reactivity in vivo was expressed as the values of specific airway resistance calculated by Pennock. Changes in ASM reactivity in vitro were tested by a tissue bath method. We found that both openers of potassium channels inhibit the citric acid-induced cough. ASM reactivity in vivo was significantly abolished by pinacidil and NS1619, which corresponded with the results of in vitro measurements. Pretreatment by selective blockers, K+ATP--glibenclamide and BK+Ca-tetraethylammonium prevented the above mentioned effects. The results indicate an important role of K+ATP and BK+Ca ion channels in defense reflexes of airways.