In the vertebrate retina, the light responses of post-receptor neurons depend on the ambient or background illumination. Using intracellular recording, we have found that a circadian clock regulates the light responses of dark-adapted fish cone horizontal cells. Goldfish were maintained on a 12-hr light/12-hr dark cycle. At different times of the day or night, retinas were superfused in darkness for 90 min ("prolonged darkness"), following which horizontal cells were impaled without the aid of any light flashes. The vertebrate retina is able to respond to visual images in starlight, in the midday sun, and at all times in between, during which the ambient or background illumination changes by 6 to 12 orders of magnitude (1, 2). This ability derives from the presence of two kinds of photoreceptor cells, rods and cones, which subserve nighttime and daytime vision, respectively, and from at least two kinds of adaptive mechanisms. The first kind of adaptive mechanism, photoreceptor adaptation, is determined by the relative degree of visual pigment bleached or regenerated in photoreceptors (3) and by the regulatory role of Ca2+ in the phototransduction process (4). The second adaptive mechanism, network or neural adaptation, is determined by post-receptor cellular and synaptic mechanisms of retinal networks or circuits (3).Network adaptation likely underlies various reported changes in the light responses of post-receptor neurons that depend on the ambient illumination, including changes in the center-surround receptive field organization of ganglion cells (5, 6) and in the light responsiveness of horizontal cells, a type of second order cell (7). In nonmammalian vertebrates dark adaptation increases rod, and decreases cone, input to horizontal cells and light adaptation has the opposite effects (8, 9).A circadian clock is a type of biological oscillator that has persistent rhythmicity with a period of approximately 24 hr in the absence of external timing cues (e.g., constant darkness). In addition, a circadian clock can be entrained by cyclic environmental stimuli, such as light (10). In vertebrate retinas, a variety of cellular phenomena are regulated by circadian rhythms, including melatonin production and release (11, 12), tyrosine hydroxylase activity (13) Intact, isolated retinas were superfused at 0.5 ml/min with a Ringer's solution that contained 130 mM NaCl, 2.5 mM KCl, 20 mM NaHCO3, 0.7 mM CaCl2, 1.0 mM MgCl2, and 20 mM glucose, as described (22,23). Oxygenation of the superfusate with a mixture of 95% 02/5% CO2 maintained the superfusate at a pH of 7.4 in the retinal chamber. After surgery, the retinas were superfused in darkness for 90 min ("prolonged darkness"), following which a horizontal cell was impaled without Abbreviation: ZT, Zeitgeber.