The steps that intervene between the absorption of a photon and the flow of electrical current across the photoreceptor cell membrane is being studied to enumerate the chemical changes that follow the isomerization of the visual pigment. The molecular mechanisms by which the reaction products change the conductance of the photoreceptor cell membrane, and the way in which the properties of the photoreceptor cell membrane affect the generation of photocurrent are being examined. Several clues that promise to help unravel the problem of photoexcitation are being investigated. One important clue is that in both vertebrate and invertebrate photoreceptors, calcium plays a key role in photoexcitation. Using the ventral photoreceptor of the horseshoe crab, Limulus, we will use the effects of changes in extracellular and intracellular calcium on response latency as a tool to uncover the cellular and biochemical mechanisms of photoexcitation. Using isolated vertebrate outer segments we will examine the physiology of these important cellular subunits and the role of internal and external calcium in their function by methods of intracellular microelectrode penetration.