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Animal behaviors are often composed of distinct alternating behavioral states. Neuromodulatory signals are thought to be critical for establishing stable behavioral states and for orchestrating transitions between them. However, we have only a limited understanding of how neuromodulatory systems act in vivo to alter circuit performance and shape behavior. To address these questions, we have investigated neuromodulatory signaling in the context of Caenorhabditis elegans egg-laying. Egg-laying activity cycles between discrete states–short bursts of egg deposition (active phases) that alternate with prolonged quiescent periods (inactive phases). Here using genetic, pharmacological and optogenetic approaches for cell-specific activation and inhibition, we show that a group of neurosecretory cells (uv1) located in close spatial proximity to the egg-laying neuromusculature direct the temporal organization of egg-laying by prolonging the duration of inactive phases. We demonstrate that the modulatory effects of the uv1 cells are mediated by peptides encoded by the nlp-7 and flp-11 genes that act locally to inhibit circuit activity, primarily by inhibiting vesicular release of serotonin from HSN motor neurons. This peptidergic inhibition is achieved, at least in part, by reducing synaptic vesicle abundance in the HSN motor neurons. By linking the in vivo actions of specific neuropeptide signaling systems with the generation of stable behavioral outcomes, our study reveals how cycles of neuromodulation emanating from non-neuronal cells can fundamentally shape the organization of a behavioral program., Author summary Animals have robust mechanisms in place to shape their behavior in a manner that is beneficial both for their survival and for the survival of their progeny. A class of signaling molecules known as neuropeptides have been implicated in driving transitions between behavioral states but we have only a limited understanding of how neuropeptide signaling modulates neural circuit activity in vivo to elicit alternate behavioral outcomes. Egg-laying behavior in the model system C. elegans cycles between clusters of egg-laying and prolonged inactive periods. This temporal organization provides for spatial dispersal of eggs, presumably benefiting progeny by limiting local overcrowding and competition for food. Here we uncover a novel neuromodulatory mechanism that shapes the timing of egg-laying behavior. Specifically, we find that neuromodulatory signaling from a group of non-neuronal cells specifies transitions between active and inactive phases of egg-laying by regulating neurotransmitter release from the motor output neurons of the egg-laying circuit. Advancing our knowledge of how neuropeptides and other modulators act in the context of the circuits in which they are endogenously released will be critical in ongoing efforts to understand how alternate behavioral states, for example those underlying mood or arousal, are encoded.