Capsaicin, a lipophilic alkaloid, blocked type I K+ currents in rabbit cultured Schwann cells when applied by superfusion. The concentration-response relation at equilibrium was well described by a rectangular hyperbola, with a K(D) of 8.7 mum. The kinetics of block resembled an 'inactivation', the rate of blockade increasing with increasing concentrations of capsaicin (1-100 mum). Unlike internal tetraethylammonium (TEA) ions (5-10 mm), which preferentially reduced outward current in symmetrical high [K+], capsaicin reduced both inward and outward type I current by the same proportion. The block achieved by capsaicin during a voltage-clamp step that activated the current was relieved by subsequent hyperpolarization, and the rate of relief from block at -70 mV and -100 mV could be reasonably accounted for on the assumption that capsaicin had to unbind to allow the channels to close.