Although much is known about the underlying mechanism of endothelium-dependent flow-induced vasorelaxation, the cellular processes responsible for the endothelium-independent flow-induced relaxation observed in some vessels is unknown. As there is evidence for the participation of K<sup>+</sup> channels in the endothelium-dependent response, the present study was designed to determine whether such channels are involved in the endothelium-independent response and if so, which ones. We examined the effects of various selective K<sup>+</sup> channel blockers on endothelium-independent relaxation initiated by intraluminal flow (10–80 µl/min), and by an endothelium-independent vasodilator sodium nitroprusside (SNP, 1 nmol/l to 3 µmol/l) in segments of the rabbit facial vein under isometric conditions. Flow-initiated relaxation was abolished by 25 and 40 mmol/l K<sup>+</sup> as well as 10 mmol/l tetraethylammonium (TEA), significantly inhibited by 100 µmol/l Ba<sup>2+</sup>, 5 mmol/l Cs<sup>+</sup> and 7.5 mmol/l 4-aminopyridine (4-AP), but unaffected by 5 µmol/l glibenclamide and 50 nmol/l charybdotoxin. Relaxation induced by SNP was reduced by 7.5 mmol/l 4-AP, but not by any of the above drugs in their listed concentrations. The inhibitory effect of 100 µmol/l Ba<sup>2+</sup> on the relaxation caused by low concentrations of K<sup>+</sup> (15–20 mmol/l) supports the presence of inward rectifier K<sup>+</sup> channels in the vascular smooth muscle cells of this tissue. We speculate that endothelium-independent flow-initiated relaxation of the rabbit facial vein may be associated with activation of inward rectifier and voltage-dependent K<sup>+</sup> channels. The latter may also contribute to the vasorelaxation initiated by SNP.