1. Whole-cell and single-channel currents were recorded together with intracellular Ca2+ in voltage clamped, single endothelial cells isolated from human umbilical vein. 2. The major current component under resting conditions in the whole-cell configuration was a strongly inwardly rectifying potassium current. 3. This current is due to activation of a K+ channel with an inward conductance of 29 +/- 3 pS (n = 7) with symmetrical 140 mM K+ on both sides of the membrane. This channel could be measured both in the cell-attached and in the inside-out configuration. At potentials below -110 mV both whole-cell and averaged single-channel currents showed a fast inactivation. 4. During stimulation of endothelial cells with histamine, whole-cell K+ currents initially increased but then substantially declined, despite the sustained increase in intracellular Ca2+ concentration ([Ca2+]i). 5. The blockade of the inwardly rectifying K+ channel by histamine could not be observed in cell-attached patches if histamine was added to the bath. 6. It is concluded that endothelial cells possess K+ channels that are directly inhibited by agonists, such as histamine. Blocking these channels may depolarize the cell membrane and thereby reduce the driving force for Ca2+ influx.