Human red blood cells (RBC) can be studied by means of whole-cell and nystatin-perforated patch-clamp techniques. In 85% of the whole-cell experiments (n = 86) and 69% of the perforated-patch recordings (n = 13), steps to positive potentials, from a holding potential of 0 mV, induced a slow-activating non-inactivating persistent outward current which reverted at about 0 mV The current activation phase fitted well with a two-component exponential curve. Half-maximal conductance was reached at about 42 mV. Na+ and K+ carried this current, which was not affected by 20 nM charybdotoxin or 20 mM TEA, but was reduced following a partial substitution of extracellular Cl- by tartrate. This current has characteristics similar to the single-channel currents already described in RBC and may be involved in the rapid adaptations of these cells in the circulation. (C) 2003 Elsevier B.V. All rights reserved.