Dopamine reaches targets in the outer retina of the clawed frog (Xenopus laevis) by diffusion from a network of dopaminergic cells and processes located predominantly at the junction of inner nuclear and inner plexiform layers. We obtained values for the steady-state release, uptake, and extracellular concentration of dopamine in the retina by a combination of HPLC (with electrochemical detection), scintillation spectroscopy, and fast-scan cyclic voltammetry. Vitreal concentrations of dopamine varied from 564 ± 109 nM in light-adapted eyes near the time of subjective dawn to 156 ± 12 nM in dark-adapted eyes. The data are consistent with a simple model for steady-state dopamine diffusion from an appropriately sited thin-sheet source. This model was used to generate a profile of extracellular dopamine concentration as a function of retinal depth. The model predicted an increase in the dopamine concentration from the vitreous to the layer of dopaminergic cells, remaining constant from that layer to the distal tips of the photoreceptors. This prediction was borne out by comparing fast-scan voltammetric measures of dopamine at the distal tips of the receptors with the vitreal concentrations determined by HPLC using electrochemical detection.In the vertebrate retina, dopamine has been implicated in a host of processes, including modulation of neural circuitry (1-4), light and dark adaptation (5), photomechanical movements (6), and circadian rhythmicity (7). The sole source of dopamine in the retina is a subclass of amacrine or interplexiform cell (8). Thus in all vertebrates except fishes, the great majority of dopaminergic processes are confined to the inner retina (9), yet there is clear evidence that outer retinal cells-i.e., photoreceptors, horizontal cells, and cells of the retinal pigment epithelium, located 10-100 ,um from the layer of dopaminergic neurons-have receptors for dopamine (10)(11)(12). On this basis it has been postulated that dopamine reaches these targets by diffusion (11), thus exemplifying a "local hormone" or volume transmission mode of communication (13 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. located 2 m above the tank provided about 30 puW/cm2 at the surface of the water. Dark-adapted eyes were obtained from frogs kept overnight in a light-tight container and sacrificed under dim red light.To measure vitreous dopamine, dark-or light-adapted eyes were flash frozen on dry ice immediately after enucleation, and the frozen vitreous bodies were dissected free of adherent tissues under a microscope. A 10-,ld aliquot of deionized water containing 0.004% ascorbate was added to each sample. The isolated vitreous bodies were stored at -80°C until analyzed by HPLC with electrochemical detection (ED) using an ESA (Bedford, MA) model 5100 coulometric electrochemical detector equipped with a model 5011 dualelectrode high-sensitivit...