Most neurons of area 17 in the cat respond to both light and dark stimuli, and it is often assumed that these responses originate from the on-center and off-center cells, respectively, of the lateral geniculate nucleus. This has not been demonstrated experimentally, however. Whether the on and off pathways make unique contributions to some of the response properties characteristic of visual cortex, such as orientation selectivity, is also unknown. The aim of these experiments was to investigate these questions by inactivating the retinogeniculate on pathway. In cats in which D,L-2-amino-4- phosphonobutyric acid (APB) had been injected into one eye, we found that, in the geniculate layers driven by that eye, there were no cells with on-center responses (Horton, J. C., and H. Sherk (1984) J. Neurosci. 4: 374–380). The on pathway appeared to have been inactivated. To see how cortical receptive fields were affected, we examined 184 binocular cells in area 17 contralateral to the injected eye. Each cell still had a normal receptive field in the ipsilateral eye, and we compared the cell's response properties in that eye with those in the eye injected with APB to assess the drug's effects. Overall responsiveness in the injected eye was severely reduced, and responses to the onset of stationary light stimuli were almost entirely abolished. Responses to moving light edges were weak or absent in most cells but still strong in a few; simple cells tended to have more vigorous light edge responses than complex cells. The general reduction in responsiveness, and the specific reduction in light edge responses, indicated that the on and off pathways both contribute (directly or indirectly) to the responses of most cells in area 17. The remaining responses to light edges we think originated mainly from the on- surrounds of off-center geniculate cells. Responses to moving dark edges were somewhat depressed compared to those in the normal eye. There was, however, no systematic change in direction selectivity and no reduction in specificity for orientation or length. In general, receptive field properties remained surprisingly normal despite the conspicuous reduction in responsiveness.