The neuroendocrine axes of the central nervous system (CNS) of an organism regulate most of the body's functions, and they in turn are under precise control by exogenous and endogenous stimuli. There is a relative dearth of knowledge of the mechanisms by which different stimuli control neurosecretion. Thus the objective of this research is to understand the mechanisms by which regulatory stimuli act via the CNS to control neurosecretion. This basic knowledge could theoretically be used to develop methods with which to manipulate the function of the system. Vertebrate neuroendocrine models have had limited usefulness in studies of extrinsic and intrinsic regulation of neurosecretion because of their structural and functional complexity. Invertebrates are currently providing the models of choice, and insects are potentially excellent models because their neuroendocrine systems are fairly simple and are directly entrained by primary exogenous stimuli like photoperiod. The principal cerebral neuroendocrine axis in the insect is that which produces the prothoracicotropic hormone (PTTH), the primary effector of insect postembryonic development. In the tobacco hornworm, Manduca sexta, the unicellular PTTH neuroendocrine axis releases PTTH in response to both circadian and seasonal photoperiod cycles. The seasonal photoperiodic cue curtails PTTH release resulting in arrested development of the pupa, termed diapause. The brain of Manduca is directly sensitive to this photoperiodic input, possessing the photoreceptor, photoperiodic clock and neuroendocrine effector. Since the secretion of PTTH can be programmed in vitro by different light: dark cycles, a system exists with which regulation of neurosecretion in the CNS by photoperiod can be investigated directly in vitro. This study proposes: 1) to elucidate the physiology of PTTH secretion; 2) to identify the neurotransmitters controlling the prothoracicotropes; 3) to localize in the brain the photoperiodic clock and photoreceptor; 4) to delineate the effects of photoperiodic reprogramming on the neurochemistry and neurophysiology of the PTTH axis; and 5) to assess the effects of photoperiodic reprogramming on the biosynthesis of PTTHs. Contemporary neurobiological techniques will be employed in the accomplishment of these objectives. The basic information these studies should provide about the photoperiodic regulation of a neuroendocrine axis will make it possible to investigate directly the molecular mechanisms(s) by which exogenous and endogenous regulation of neurosecretion occurs.