The THP-1 human monocytic leukemia cell line is a useful model of macrophage differentiation. Patch clamp methods were used to identify five types of ion channels in undifferentiated THP-1 monocytes. (i) Delayed rectifier K+ current, IDR, was activated by depolarization to potentials positive to -50 mV, inactivated with a time constant of several hundred msec, and recovered from inactivation with a time constant approximately21 sec. IDR was inhibited by 4-aminopyridine (4-AP), tetraethylammonium (TEA+), and potently by charybdotoxin (ChTX). (ii) Ca-activated K+ current (ISK) dominated whole-cell currents in cells studied with 3-10 micron [Ca2+]i. ISK was at most weakly voltage-dependent, with reduced conductance at large positive potentials, and was inhibited by ChTX and weakly by TEA+, Cs+, and Ba2+, but not 4-AP or apamin. Block by Cs+ and Ba2+ was enhanced by hyperpolarization. (iii) Nonselective cation current, Icat, appeared at voltages above +20 mV. Little time-dependence was observed, and a panel of channel blockers was without effect. (iv) Chloride current, ICl, was present early in experiments, but disappeared with time. (v) Voltage-activated H+ selective current is described in detail in a companion paper (DeCoursey & Cherny, 1996. J. Membrane Biol. 152:2). The ion channels in THP-1 cells are compared with channels described in other macrophage-related cells. Profound changes in ion channel expression that occur during differentiation of THP-1 cells are described in a companion paper (DeCoursey et al., 1996. J. Membrane Biol. 152:2).