Secretoneurin is a newly discovered peptide found in high concentrations in brain. We have studied the release of secretoneurin and noradrenaline from superfused hypothalamic slices from rat brain. Both electrical stimulation and potassium induced depolarisation released secretoneurin and noradrenaline from these slices in a calcium-dependent manner. Electrical stimulation caused a preferential release of noradrenaline when compared to the secretion elicited by high potassium. The time course of secretoneurin release was more protracted than that of noradrenaline. The calcium channel blocker omega-conotoxin inhibited only the electrically induced release of noradrenaline, whereas nifedipine inhibited only that of secretoneurin. These results establish that secretoneurin is secreted from neurons. Inhibition of this release by nifedipine is consistent with the concept that secretion from large dense core vesicles occurs at sites different from that of small vesicles and depends on calcium influx via L-type calcium channels.