Hatchling chicks reared with defocusing spectacle lenses compensate for the applied defocus, both refractively and through changes in eye growth, in about 1 week. In this experiment, we show that pharmacological inhibition of the retinal ON or OFF responses to light stimulation with isomers of alpha-aminoadipic acid results in a sign-dependent pattern of interference with the refractive compensation mechanism. An intravitreal injection of 2.5 microM L-alpha-aminoadipic acid inhibited the ERG ON response and inhibited refractive compensation to negative lens defocus, but not to positive or zero power lens defocus. D-alpha-aminoadipic acid in the same dose reduced the retinal OFF response and inhibited refractive compensation to positive lens defocus, but not to negative or zero power lenses. Thus the pharmacological manipulation of induced refractive change suggests that the retinal ON and OFF subsystems play independent roles in the emmetropization process.