To investigate whether apoptosis plays a role in traumatic brain injury (TBI), we examined the expression of Bcl-2 and Bax proteins and the release of mitochondrial cytochrome c in rat brains using Western blot analysis. Bcl-2 at the predicted 26 kDa was not detected in controls and TBI groups. However, at 1 h post-TBI, a shortened Bcl-2 protein with a molecular size of similar to 14.5 kDa was detected in the injured hemisphere (R). At 4 and 12 h post TBI, an additional bcl-2 band (similar to 10 kDa) was detected in R. Both bands disappeared at 14 days postinjury. The predicted 21-kDa band of Bax was detected in both controls and TBI animals. In addition, two shortened Bax proteins (similar to 18 kDa) were detected after TBI. The time course of appearance was similar to that of Bcl-2 described above. In the present study, neither cytochrome c release from mitochondria nor DNA fragmentation was detected in the forebrains of sham and TBI groups. Treatment of animals with an antioxidant N-acetylcysteine administered ip greatly diminished the levels of shortened Bcl-2 and Bax proteins. These findings suggest that the induction of shortened Bcl-2 and Bax proteins in rat brains may be associated with reactive oxygen species generated after TBI.