The role of the vesicle priming factor CAPS (calcium-dependent activator protein for secretion) in somatic exocytosis was studied in the large serotonergic Retzius neuron of the leech. Increased electrical activity prompts Retzius neurons to release serotonin en masse from somatic dense core vesicles (DCVs). This exocytosis is evoked by calcium release from intracellular stores, indicating that the molecular fusion complex differs from that at synapses and is more similar to that in endocrine cells. The search for candidate proteins that promote DCV fusion began in the Retzius neuron-specific transcriptome. The high level of leech CAPS (Hve-CAPS1) mRNA in the transcriptome was confirmed by in situ hybridization in leech central ganglia. Dense staining developed in the somata of Retzius and other neuronal types. Immunostaining revealed accumulation of the protein in the soma shell and the nuclear periphery. The role of Hve-CAPS1 in exocytosis was tested by knocking it down via injection of synthetic interfering RNA (siRNA) into cultured neurons. Exocytosis was stimulated with 40 mM potassium and measured using fluorescent FM1-43 staining of vesicles during exo/endocytosis cycles. Knocking down Hve-CAPS1 resulted in a 51.6% decrease in somatic FM1-43 spots compared to the control group, indicating an equivalent reduction in vesicle clusters undergoing fusion. The contribution of Hve-CAPS1 to DCV priming introduces a highly regulated priming step into the conserved mechanism of somatic exocytosis in neurons.