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1Ro 31-6930 (0.001-0.3 MM), cromakalim (0.03-3.0OUM), salbutamol (0.001-0.3 pM) and theophylline (0.3-100pM) evoked dose-related reductions in guinea-pig spontaneous tracheal tone with IC,0 values of 0.044, 0.20, 0.021 and 21.OpM respectively. All four agents also relaxed tone supported by betahistine, carbachol, 5-hydroxytryptamine (5-HT), leukotriene D4 (LTD4), U46619 and prostaglandin D2 (PGD2). The order of potency of tracheal relaxants was always salbutamol > Ro 31-6930 > cromakalim > theophylline. 2 All four agents evoked dose-related reductions in 5-HT-and histamine-induced bronchoconstriction in pithed vagotomised guinea-pigs. The dose of Ro 31-6930 producing 50% inhibition of a 5-HT bronchoconstriction was 11.6 pgkg-' and the dose producing 50% inhibition of a histamine bronchoconstriction was 4.4pgkg-. Salbutamol was approximately 4-5 times more potent than Ro 31-6930 whilst cromakalim was approximately 10 times less potent than Ro 31-6930 as a bronchodilator. Theophylline was markedly less potent than any of the other agents. 3 Ro 31-6930, cromakalim, salbutamol and theophylline each protected conscious guinea-pigs from histamine-induced respiratory distress. Ro 31-6930 and salbutamol were each effective at oral doses of 1.0 and 3.Omgkg-1 whilst cromakalim was effective at oral doses of 3.0 and 10.0mgkg-'. Theophylline showed activity only at 300 mg kg-1 p.o. 4 Ro 31-6930 is a novel potassium channel opener which is a potent relaxant of guinea-pig tracheal smooth muscle in vitro and a bronchodilator in vivo.