1. BRL 55834, a novel potassium channel activator, has been compared with levcromakalim (BRL 38227) for its relaxant effects in vivo on the airways and vasculature of the guinea-pig and rat. 2. When administered intravenously 2 min prior to challenge, BRL 55834 and levcromakalim each inhibited histamine-induced increases in airways resistance (Raw) in the anaesthetized guinea-pig, with BRL 55834 showing a 4.5 fold greater potency than levcromakalim (ED25 = 2.5 micrograms kg-1 and 11.3 micrograms kg-1 respectively). By contrast, both compounds had similar hypotensive potencies (ED18 = 8.5 micrograms kg-1 and 6.5 micrograms kg-1 respectively). 3. In the same guinea-pig model, intraduodenally administered BRL 55834 (100 and 250 micrograms kg-1) and levcromakalim (500 micrograms kg-1) each protected against histamine-induced changes in Raw and dynamic lung compliance (Cdyn), both compounds showing a rapid onset of action that persisted for more than 50 min. The lower dose of BRL 55834 had a similar bronchodilator effect to that of levcromakalim, yet both doses of BRL 55834 elicited substantially smaller effects than levcromakalim on mean arterial blood pressure. 4. In the anaesthetized rat, BRL 55834 and levcromakalim each evoked a dose-related inhibition of inhaled methacholine-induced changes in Raw and Cdyn when given i.v., with BRL 55834 showing some four fold greater potency than levcromakalim (BRL 55834: Raw ED35 = 3.7 micrograms kg-1, Cdyn ED35 = 5.9 micrograms kg-1; levcromakalim: Raw ED35 = 16 micrograms kg-1, Cdyn ED35 = 23.5 micrograms kg-1). As in the guinea-pig,BRL 55834 had a reduced propensity to lower mean arterial blood pressure (ED11 = 8 microg kg-1 for BRL55834, 11 +/- 3% being its maximum effect; ED11= 16 microg kg-1, maximum effect= 34 +/- 6% for levcromakalim.5. When administered intraduodenally to anaesthetized rats, BRL 55834 (10, 20 and 100 microg kg-1)evoked rapid and dose-related inhibitions of methacholine-induced Raw and Cdyn changes which persisted for over 30 min. At the lower and middle dose there was little effect on mean arterial blood pressure(<10% fall). Levcromakalim (500 microg kg-1) by contrast elicited transient airways responses that diminished rapidly after 5 min, while the effects on blood pressure were well maintained (>20% at 65 min). Levcromakalim (100 microg kg-1) did not affect airways responses but also evoked a marked and sustained fall in blood pressure.6. BRL 55834, administered per os, prolonged the time to histamine-induced dyspnoea in conscious guinea-pigs. The greatest effect of BRL 55834 was observed when it was administered 60 min prior to challenge, a dose of 0.20 mg kg-1 doubling the mean time to collapse. A similar level of protection was afforded by levcromakalim (1.25 mg kg-1), with maximal activity occurring between 30 and 60 min.7. The present studies in guinea-pigs and rats indicate that BRL 55834 is the first potassium channel activator to exhibit greater bronchodilator potency than levcromakalim but reduced tendency to lower arterial blood pressure. It is suggested that BRL 55834 may have greater potential than levcromakalim as a bronchodilator for therapeutic use in man.