The effects of a decrease of the K+ gradient on the extraneuronal inward transport and outward movement of catecholamines were studied in rat heart, rabbit aortic rings and guinea-pig trachealis smooth muscle. Elevation of the extracellular K+ concentration caused a) inhibition of the corticosteroid-sensitive extraneuronal uptake (uptake2) of 3H-isoprenaline in rat heart and of 3H-noradrenaline in rabbit aorta, and b) acceleration of efflux of 3H-isoprenaline from rat heart, 3H-noradrenaline from rabbit aorta and adrenaline (measured by microphotometry) from guinea-pig trachealis muscle. In rat heart and rabbit aorta, the acute omission of one or the other of the ions Na+, Cl-, K+ or Ca2+ from the perfusion of incubation medium had no effect on initial rates of uptake2 of catecholamines, except that the absence of K+ had a small inhibitory effect in the rat heart. The prolonged absence of Na+, Ca2+ or K+ from the perfusion or incubation medium caused a marked inhibition of uptake2 of catecholamines. These inhibitory effects developed more quickly in rat heart than in rabbit aorta. These results are compatible with the possibility that either the K+ gradient across the cell membrane or the resting membrane potential is the force driving uptake2.