The tree shrew Tupaia belangeri has three functional pathways (ON‐center, OFF‐center, and W‐like cells) that arise in the retina and proceed through separate LGN laminae to separate cortical targets. To determine whether these pathways have consistent differences in activity, cytochrome oxidase (C.O.) patterns were examined in the retina, LGN, and striate cortex. In six normal tree shrews the outer and inner plexiform layers of the retina were highly reactive for C.O. A pale, vascularized cleft zone separated the a (OFF) and b (ON) inner plexiform sublaminae, which seemed about equally reactive for C.O. In the LGN, laminae 1 and 2 (ON‐center cells) and laminae 4 and 5 (mostly OFF‐center cells) were highly reactive for C.O. LGN lamina 3 and 6 are part of an W‐like afferent pathway. Lamina 3 was distinctly paler than laminae 1, 2, 4, and 5 while lamina 6 was intermediate. In the striate cortex, layer IV was the most reactive layer. Sublayer IVb (predominantly an OFF region) was consistently more reactive than sublayer IVa (predominantly ON). The middle portion, layer IVm, was paler than either IVa or IVb. This pale region includes, but extends above and below, the cell‐sparse “cleft” region. Thus, considering all three levels of the retinogeniculostriate pathway, the ON and OFF systems were equally active until they reached the striate cortex, where the OFF system appeared to be more active than the ON. The W‐cell laminae in the LGN exhibited the lowest level of activity. The contribution of ganglion cell activity to these patterns was assessed by intravitreal administration of tetrodotoxin (TTX) blockade either monocularly (three animals) or binocularly (two animals). In the TTX‐treated retinae, the inner plexiform a and b sublaminae were paler for C.O., although visible, and were still separated by the pale cleft. The ganglion cell layer was very pale in comparison to the normal. In the LGN, monocular TTX blockade reduced the C.O. reactivity in the ON and OFF laminae that received input from the treated eye but had little effect on the W‐like cell laminae. The ipsilaterally innervated ON and OFF laminae were more affected than were the contralaterally innervated laminae. Binocular TTX treatment resulted in a decrease of C.O. activity in the binocular segment of the ON and OFF LGN laminae. In the striate cortex, the most marked changes following TTX treatment occurred in layer IV. As in the LGN, the effects of monocular TTX were greater ipsilaterally than contralaterally. In the hemisphere contralateral to the treated eye, sublayers IVa and IVb were paler than the normal but the general pattern remained the same. Ipsilateral to the TTX‐treated eye, the decrease in C.O. reactivity was especially marked in lower IVa and upper IVb adjacent to IVm, giving the appearance that the middle pale zone had widened. Bilateral TTX also reduced the reactivity in layer IV. However, the pattern resembled that seen ipsilateral to monocular TTX treatment. In all cases, whether monocular or binocular TTX, sublayer IVb remained slightly more reactive than IVa. Four saline control animals showed basically normal C.O. patterns throughout the visual system, as did three animals that recovered for 2 months after 2 weeks of TTX administration. The TTX‐produced reduction in C.O. activity in the striate cortex suggests a model of geniculocortical input in which (1) ipsilateral eye inputs to layer IVa and IVb produce a greater postsynaptic C.O. activity level in the lower portion of IVa and the upper portion of IVb adjacent to IVm; (2) contralateral‐eye inputs predominate in producing the C.O. activity in upper IVa and lower IVb; and (3) the ipsilateral pathway suffers a greater decrease in activity following retinal impulse blockade than does the contralateral pathway. Copyright © 1988 Alan R. Liss, Inc.