Stimulus-secretion coupling studies were carried out on adrenal chromaffin tissue from the toad. Catecholamine (CA) secretion was generated in response to acetylcholine (ACh) or high K+. 2. The response to ACh was found to be dependent on the presence of external Ca2+. The secretion induced by ACh or high K+ was inhibited by the Ca-channel blockers CoCl2 and nifedipine. 3. The specific Na+/H+ ionophore, monensin, induced a strong secretory response only if Na+ was present in the Ringer. Monensin's effect did not depend on external Ca2+ and was unaffected by the channel blockers tetrodotoxin or CoCl2. 4. Secretion induced by monensin was exocytotic as was shown by measuring ATP release using a photoluminescence, luciferine/luciferase assay. 5. In conclusion, in the toad, as in higher species, stimulus-secretion coupling involves Ca2+ entry from the external medium, possibly through voltage-dependent channels. Monensin is a potent secretagogue and the mechanism by which the ensuing elevation of intracellular Na+ concentration might induce a secretory response remains to be determined.