Endothelial cells obtained from human umbilical chord have been studied by the patch clamp method. An ion channel is described that is activated by microM concentrations of histamine and shows a slow run-down in cell-attached patches. After excision, channel activity quickly runs down to zero open probability. In symmetrical potassium concentrations (140 mM K in the bath and the pipette), the single channel conductance is 28 +/- 2 pS and the reversal potential is 0.3 +/- 0.8 mV (mean +/- SEM, n = 4). With 140 mM Na in the pipette, the conductance is 26 +/- 2 pS. A reversal potential of -1.5 +/- 0.9 mV (n = 7) was measured. With 60 mM Ca and 70 mM Na in the pipette, 140 mM K in the bath, the reversal potential was -11 +/- 3 mV, the single channel conductance in 16 +/- 3 pS (n = 5). The single channel conductance in 110 mM Ca (pipette) and 140 mM K (bath) is 8 +/- 2 pS and the reversal potential is -18 +/- 6 mV (n = 3). From analysis of the reversal potentials, a permeation ratio of K:Na:Ca = 1:0.9:0.2 was calculated. This ligand-gated non-selective cation channel in human endothelial cells is Ca permeable and could induce a sustained agonist mediated Ca influx.