Hybrid seedlings from reciprocal interspecific crosses between Nicotiana nudicaulis and N. tabacum were not viable when cultured at 28 degrees C; this an example of hybrid lethality. Characteristically, shoot apices and root tips of these hybrids began to brown immediately after germination at 28 degrees C. However, hybrid seedlings did not exhibit any symptoms of lethality at 34 degrees C, and their growth was normal at this higher temperature. When hybrid seedlings were cultured at 34 degrees C and then transferred to 28 degrees C, lethal symptoms emerged rapidly after the transfer. Therefore, hybrid lethality associated with reciprocal interspecific crosses between N. nudicaulis and N. tabacum was due to the interaction of coexisting heterologous genomes and not to a cytoplasmic effect. Furthermore, as the N. nudicaulisXN. tabacum seedlings die, features of apoptotic cell death, including chromatin condensation, nuclear fragmentation, and fragmentation of DNA, were evident. These observations indicated that hybrid lethality of N. nudicaulisXN. tabacum seedlings is accompanied by apoptotic cell death. This report is the first to demonstrate that hybrid lethality with apoptotic cell death results from N. nudicaulisXN. tabacum hybridization.