Intracerebral transplants of ventral mesencephalic (VM) tissue have been well characterized. VM grafts contain numerous tyrosine hydroxylase immunoreactive neurons which send axons into the host brain. Transplanted neurons in VM grafts develop normally in that they contain tyrosine hydroxylase and GAP43. An overlooked aspect of graft development is cell death. It has been suggested that cell death in VM grafts was mostly necrotic. However, recent work in this laboratory suggested that developing grafts contain numerous apoptotic cells. In the present paper morphological, histochemical, and molecular correlates of apoptosis were used to assay cell death during VM graft development. At early times (5-15 days) after grafting VM grafts contained numerous apoptotic cells. In older grafts (21 and 28 days) few apoptotic cells were observed. In situ end labeling of fragmented DNA with biotinylated dUTP showed that early grafts contained numerous positive cells. The expression of RP8, a molecular correlate of apoptotic cell death, occurred in early grafts, but was not detectable in older grafts. These results indicate that apoptosis is a normal part of VM graft development. As in naturally developing neural systems, cell death in grafts may function to eliminate cells that fail to connect to appropriate targets.