Abstract Aim: Potassium (K+) released from contracting skeletal muscle is considered a vasodilatory agent. This concept is mainly based on experiments infusing non-physiological doses of K+. The aim of the present study was to investigate the role of K+ in blood flow regulation. Methods: We measured leg blood flow (LBF) and arterio-venous (A-V) O2 difference in 13 subjects while infusing K+ into the femoral artery at a rate of 0.2, 0.4, 0.6 and 0.8 mmol min−1. Results: The lowest dose increased the calculated femoral artery plasma K+ concentration by approx.1 mmol L−1. Graded K+ infusions increased LBF from 0.39 ± 0.06 to 0.56 ± 0.13, 0.58 ± 0.17, 0.61 ± 0.11 and 0.71 ± 0.17 L min−1, respectively, whereas the leg A-V O2 difference decreased from 74 ± 9 to 60 ± 12, 52 ± 11, 53 ± 9 and 45 ± 7 mL L−1, respectively (P < 0.05). Mean arterial pressure was unchanged, indicating that the increase in LBF was associated with vasodilatation. The effect of K+ was totally inhibited by infusion (27 mol min−1) of Ba2+, an inhibitor of Kir2.1 channels. Simultaneous infusion of ATP and K+ evoked an increase in LBF equalled to the sum of their effects. Conclusions: Physiological infusions of K+ induce significant increases in resting LBF, which are completely blunted by inhibition of the Kir2.1 channels. The present findings in resting skeletal muscle suggest that K+ released from contracting muscle might be involved in exercise hyperaemia. However, the magnitude of increase in LBF observed with K+ infusion suggests that K+ only accounts for a limited fraction of the hyperaemic response to exercise.