The patterns of cell death and of macrophages were investigated in the forebrain and eyes of the tree shrew Tupaia belangeri during five phases of optic cup formation. Seventeen embryos were studied. Three- dimensional reconstructions were made from one embryo of each phase. In phase 1 (V-shaped optic evagination) a midline band of cell death passes through the closing anterior neuroporus. From phases 2 (optic vesicle) to 5 (far-advanced invagination) the midline band of cell death extends in the dorsal wall of the forebrain to its rostral pole and, further, into its ventral wall. At the approximate future position of the optic chiasm this ventral pycnotic area, predicted but so far unidentified by others, is connected to a previously described second band of cell death passing through the optic anlagen. Recently, evidence has been presented that chicken embryos develop holoprosencephaly and cyclopia when ventral forebrain structures are lost secondary to experimentally induced apoptosis. Our findings in Tupaia suggest that, in cases of spontaneous malformations of this kind, such an atypical pycnotic area in the ventral telencephalon might result from the defective regulation of cell death processes during optic cup formation. In the forebrain and eyes of Tupaia, the occurrence of bands of cell death precedes the appearance of the earliest intraepithelial macrophages. From phase 3 (onset of invagination) onwards almost all of them are concentrated along the band of cell death.