1. Block by external tetraethylammonium (TEA) was examined on currents carried by potassium (K+) and sodium (Na+) through the cloned delayed rectifier K+ channel Kv2.1. 2. In the presence of high intracellular K+ and high extracellular Na+, currents through the Kv2.1. channel were carried almost exclusively by K+. In the absence of both intracellular and extracellular K+, large currents were carried by Na+ through the Kv2.1 channel. 3. External application of 30 mM TEA blocked K+ currents through Kv2.1. by 87%. The same external concentration of TEA had no effect on Na+ currents through this channel. 4. As the K+ concentration was increased between 0 and 140 mM, the percentage of current blocked by TEA progressively increased from 0 to 87%. 5. These data indicate that block of K+ channels by external TEE depends on the permeating ion. Furthermore, these data indicate that in the presence of Na+ and absence of K+, TEA does not bind to the channel, and that addition of low concentrations of K+ facilitates TEA binding.