Intrinsic optical changes (light scattering signals) occur in mammalian nerve terminals during and immediately following the arrival of the action potential. In the neurohypophysis (posterior pituitary gland), the action potential is coupled to calcium-mediated secretion of the neuropeptides oxytocin and vasopressin. This excitation–secretion coupling is intimately related to extremely rapid changes in light scattering. These optical signals provide a millisecond–time-resolved monitor of events in the terminals that follow the arrival of the action potential and the entry of calcium. Light scattering procedures are designed to measure intrinsic optical signals from mammalian nerve terminals. In practice, these signals are remarkably simple to record from any of the mammalian neurohypophyses that have been studied. To date, this approach has been used successfully in mouse, rat, and guinea pig. This protocol provides instrumentation requirements and a method for preparation of the neurohypophysis so that intrinsic optical signals can be measured from nerve terminals. It also includes a discussion of the interpretation of the signals that are obtained.