The effects of cyanide (CN) on whole cell current measured with the perforated-patch method were studied in adrenal medullary cells. Application of CN produced initially inward and then outward currents at 52 mV or more negative. As the membrane potential was hyperpolarized, amplitude and latency of the outward current (I_o) by CN became small and long, respectively. A decrease in the external Na⁺ concentration did not affect the latency for CN-induced I_o but enhanced the amplitude markedly. The CN I_o reversed polarity at 85 mV, close to the Nernst potential for K⁺, and was suppressed by the K⁺ channel blockers curare and apamin but not by glibenclamide, suggesting that I_o is due to the activation of Ca²⁺-dependent K⁺ channels. Consistent with this notion, the Ca²⁺-mobilizing agents, muscarine and caffeine, also produced I_o. Exposure to CN in a Ca²⁺-deficient medium for 4 min abolished caffeine- or muscarine-induced I_o without development of I_o, and addition of Ca²⁺ to the CN-containing solution induced I_o. We conclude that exposure to CN produces Ca²⁺-dependent K⁺ currents in an external Ca²⁺-dependent manner, probably via facilitation of Ca²⁺ influx.