During the period of natural cell death in the developing mammalian brain, both target cells and afferents have been shown to be important for neuronal survival, Here we demonstrate that afferents and targets have interactive roles in the maintenance of cells during development of the mesencephalic parabigeminal nucleus (PB) in rats. Pyknotic nuclei were counted in the PB of developing rats that received a bilateral lesion of the superior colliculus on the day of birth (W). We observed that simultaneous deafferentation and deeferentation leads to a large peak of cell death at P1-2 in all three divisions of PB. Later the rate of pyknosis decreases and a second period of elevated cell death is observed just before the complete disappearance of the nucleus at W-8. Counts of healthy neurones indicates two separate periods of increased neuronal loss. The first period occurs at P1-2, and the last and dramatic episode of cell loss at P8 leads to the disappearance of the PB. The combined effects of simultaneous target removal and deafferentation were different from the sum of the individual effects, indicating that the axonal targets and the afferents interact to control cell survival in the PB.