Using an in vitro preparation of the cat carotid body, we have characterized the release of [3H]dopamine (DA) induced by high extracellular K+. Pulse superfusion (3 min) with high K+ Tyrode solution (20-80 mM) evoked a concentration-dependent release of [3H]DA from type I cells with a threshold at about 20 mM-extracellular K+ and a plateau at about 60 mM-extracellular K+. Equivalent low extracellular Na+ concentration ([Na+]o) solutions osmotically balanced with sucrose did not induce release. The high extracellular K+ concentration ([K+]o)-evoked release of [3H]DA by type I cells was dependent on the presence of Ca2+ in the superfusion media. On prolonged (10-14 min) superfusion with high K+ Tyrode solution, the [3H]DA release evoked by 60 mM-extracellular K+ was transient, while that evoked by 30 mM-extracellular K+ was sustained. In preparations superfused for 6 min with 60 mM-extracellular K+ and zero extracellular Ca2+ concentration ([Ca2+]o) Tyrode solution, reintroduction of Ca2+ did not elicit a secretory response. Ba2+ was a potent secretagogue of [3H]DA in preparations superfused with normal and zero [Ca2+]o Tyrode solution. Additionally, Ba2+ was capable of eliciting a secretory response from type I cells in preparations previously exposed (6 min) to 60 mM-extracellular K+, whether or not [Ca2+]o was present. With regards to stimulus-secretion coupling, our results indicate that high [K+]o probably depolarizes type I cells. This effect would, in turn, activate voltage-dependent Ca2+ channels, allowing the entrance of this ion to activate the neurosecretory response.