Neurons have been counted in the isthmo-optic nucleus following lesions of the optic tectum, its main source of afferents. Late lesions, made at 10.8-12.2 days of incubation, were employed as they cause the fewest non-specific side effects. The lesions spared the isthmo-optic tract, and although they caused many retinal ganglion cells to die, the degeneration did not spread to the inner nuclear layer, which contains the target cells of the isthmo-optic fibers. Hence the effects on the isthmo-optic nucleus were due to its being deprived of afferents. Even in unoperated embryos, 60% of the isthmo-optic neurons are known to die between embryonic days 12 and 17. The tectal lesions greatly increased the cell loss ipsilaterally; this was due to cell death, since other explanations such as migration away or differential cellular shrinkage have been ruled out. The fact that additional neuronal death occurred mainly during the latter half of the period of natural cell death implies that the tectal afferents are important for the survival of the isthmo-optic neurons during this latter half, but not before.