1. The membrane response to applied histamine of cultured endothelial cells from human umbilical vein was studied by use of whole cell and single channel patch clamp techniques. A value of -27 +/- 1.4 mV was found for the resting potential under whole cell current clamp. No voltage-gated currents were seen at either the macroscopic or single channel levels. 2. At holding potentials of -20 to -40 mV, histamine evoked slow rising, long lasting whole cell inward currents. The inward current was associated with depolarization and decreased input resistance. The calcium ionophore A23187 provoked similar whole cell inward currents. 3. Single channel currents were observed in cell-attached and inside-out patches for both histamine and A23187. The single channel conductance was about 20 pS with a mean open time of 5 ms and a reversal potential of 0 mV in symmetrical potassium solutions. Internal sodium blocked outward going currents. 4. For cell-attached patches, histamine-dependent channel activity required external calcium and was also seen when histamine was present in the bath but not the pipette. Recording from inside-out patches revealed that decreases in 'internal' calcium resulted in the disappearance of channel activity. 5. The histamine-dependent inward current appears to involve calcium-dependent activation of cationic channels.