The effect of the intraperitoneal injection of lithium on the pattern of the pigment screening (PS) of the frog retina has been studied in various illumination conditions. Lithium enhances the PS pattern induced by dark and it substantially modifies the PS pattern induced by the other light conditions. The dark-induced PS pattern is very stable and might be regulated by a single factor. The PS of light-adapted frogs is easily modified by drug administration and probably depends on a variety of factors which may be affected differently by the various injected substances. The possibility that lithium, melatonin and darkness might act in the same way or on the same system which regulates the PS in dark-adaptation must not be disregarded.