SUMMARY: The effect of cromakalim on vascular reactivity was studied in rat isolated pulmonary arterial strips. Cromakalim ( (0.1-1 \mu \mathrm{M})) inhibited contractions induced by low ((20-30 \mathrm{mM}) \mathrm{KCl}) concentrations in a concentrationdependent manner. It had no effect on those elicited by (60-100 \mathrm{~mm} \mathrm{KCl}). However, a higher concentration of cromakalim ((10 \mu \mathrm{M}) ) slightly decreased ( -5 to (-10 %) ) KCl efficacy. Contractions induced by noradrenaline (NA, (0.01-1 \mu \mathrm{M}) ) and angiotensin II (AII, (0.5-50 \mathrm{nM}) ) were reduced by cromakalim ( (0.1-10 \mu \mathrm{M}) ). The maximal response to NA and AII was decreased by (54 \pm 6.4 %) and (70 \pm 5.8 %(n=5)), respectively, in the presence of (10 \mu \mathrm{m}) cromakalim. The inhibitory effect of cromakalim was not dependent on the presence of vascular endothelium. After blockade of calcium influx by verapamil ((10 \mu \mathrm{M})), cromakalim had no further effect on NA- and AII-induced contractions. Cromakalim ( (0.1-1 \mu) ) had no effect on the amplitude of the transient contraction evoked by NA and AII in (\mathrm{Ca}^{2+})-free solution. The inhibitory effect of cromakalim ((1 \mu \mathrm{M})) was reversed by glibenclamide (1-10 (\left.\mu \mathrm{M}\right)) and phentolamine (5-100 (\mu \mathrm{M}) ) which, however, did not alter the relaxant effect of verapamil ((1 \mu \mathrm{M})), papaverine ((1 \mu \mathrm{M})) or theophylline ( (1 \mathrm{mM}) ). Contractions induced by NA and AII in the presence of tetraethylammonium (TEA, (10 \mathrm{mM}) ) were also depressed by cromakalim. These results show that cromakalim is a potent anticonstrictor agent in the pulmonary circulation. As in other smooth muscles, its mechanism of action involves an interaction with potassium channels at the vascular smooth muscle cell membrane level.