In mammals binocular vision is made possible by the existence in the temporal retina of ipsilaterally projecting ganglion cells (IGCs) (with axons that do not cross the brain midline and join optic fibers from the opposite eye). To learn whether early interactions between fibers of each eye play a role in generating a mixed ipsi + contralateral projection pattern, we studied with horseradish peroxidase the origin of uncrossed retinal projections in mice that developed after one eye was destroyed at very early embryonic ages. One eye was removed on embryonic day 16 (E16; when optic fibers have grown past the chiasm bilaterally, but very few have grown into the visual centers) or on E13 or E12 (when few or no optic fibers have passed the presumptive chiasm region). Normal adult mice have a mean of 946 IGCs (range: 784-1,073) within the temporal sector of the retina, and less than 25 in the rest of the retina. In adult mice enucleated at E16, an average of 1,354 (1,215-1,484) IGCs are present within a clearly demarcated temporal sector of the remaining retina and 265 (152-312) are present throughout the rest of the retina. In both the temporal and nasal retina the excess IGCs in these mice have, generally, very small somas. In some of these mice the most peripheral part of the temporal sector contains fewer IGCs. In E12 or E13 enucleates, IGCs are also generally located in a narrow (often narrower than normal) region along the temporo-inferior retinal border, but their number is less than in normal or E16-enucleated mice: E13 enucleates have a mean of 639 cells (range: 361-875) in the temporal sector and 109 (8-275) in the rest of the retina. Following enucleation of one mouse at E12, the respective values are 349 and 31 cells. The reduction in numbers of IGCs in these mice is especially pronounced for ganglion cells with small cell bodies. These findings suggest that the development of uncrossed projections in mice depends on selective guidance mechanisms of axons from temporal retina through the chiasm. These may consist of interactions of optic axons with guidance cues distributed in the presumptive chiasm (possibly at early stages) and also of fiber-fiber guidance mechanisms, in particular between fibers from each eye.