The role of the vesicle priming factor CAPS (calcium-dependent activator protein for secretion) in somatic exocytosis of serotonin was studied in the large Retzius neuron of the leech. Increased electrical activity prompts Retzius neurons to release serotonin en masse solely from clusters of somatic dense-core vesicles (DCVs). This exocytosis is largely different from that at synapses, similar to that in endocrine cells. Therefore, the molecular complex driving DCV fusion may be composed by particular types of proteins. The search for such proteins 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, where DCVs also accumulate. The role of Hve-CAPS1 in exocytosis was tested by knocking it down via injection of cocktails of synthetic interfering RNA (siRNA) into cultured neurons. Exocytosis was stimulated by 40mM potassium depolarization and measured as fluorescent spots, each spot produced upon FM1-43 staining of a DCV cluster during exo/endocytosis cycles. Knocking down Hve-CAPS1 resulted in a 51.6% decrease in somatic FM1-43 spots compared to the control group injected with a scrambled sequence, 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.