Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of naloxone and naltrexone, two supposedly "pure" opiate antagonists. Both were shown to depress excitability and action potential production when applied in relatively high concentrations. Low naltrexone concentrations antagonized the depression produced by naloxone, but low naloxone concentrations did not antagonize the depression produced by high naltrexone concentrations. Naltrexone also depressed the stimulus-induced increase in potassium conductance (gK) which naloxone did not do. Thus, the naloxone depression is mediated via an opiate drug receptor, whereas naltrexone in high concentrations produces a "local anesthetic-like" depression not involving the opiate drug receptor.