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This study reveals that a cluster of neurons expressing the neuropeptide hugin transmit inputs from higher brain centers to motor centers, thereby regulating feeding and locomotion in fruit fly larvae., Central mechanisms by which specific motor programs are selected to achieve meaningful behaviors are not well understood. Using electrophysiological recordings from pharyngeal nerves upon central activation of neurotransmitter-expressing cells, we show that distinct neuronal ensembles can regulate different feeding motor programs. In behavioral and electrophysiological experiments, activation of 20 neurons in the brain expressing the neuropeptide hugin, a homolog of mammalian neuromedin U, simultaneously suppressed the motor program for food intake while inducing the motor program for locomotion. Decreasing hugin neuropeptide levels in the neurons by RNAi prevented this action. Reducing the level of hugin neuronal activity alone did not have any effect on feeding or locomotion motor programs. Furthermore, use of promoter-specific constructs that labeled subsets of hugin neurons demonstrated that initiation of locomotion can be separated from modulation of its motor pattern. These results provide insights into a neural mechanism of how opposing motor programs can be selected in order to coordinate feeding and locomotive behaviors., Author Summary In the animal kingdom, two of the most essential behaviors are locomotion and feeding. The motor programs underlying these behaviors are controlled by higher-order circuits in the central nervous system. However, how an organism selects a particular motor program based on inputs from the information-processing higher brain centers to generate an adaptable behavior is not well understood. Here, we analyze the behavior of Drosophila larvae after activating a small cluster of neurons in the brain and show that the animals simultaneously stop eating and start moving. These neurons express the neuropeptide hugin, which is homologous to the mammalian neuromedins. We show that the reduction of food intake depends on hugin and that the cluster of hugin neurons is functionally divided into distinct subgroups that both accelerate the motor program for locomotion and decelerate the motor program for feeding. We propose that hugin neurons represent a control system between the higher brain circuits that process information and those that execute motor programs.