WE tested the neuroprotective potential of the Bcl-220–34peptide sequence in hippocampal slices. Treatment with Bcl-2 after fluid percussion trauma significantly improved recovery of CA1 antidromic PS to a mean of 92% ± 1 of initial amplitude, compared with only 16% ± 2 in unmedicated slices. The EC50for trauma protection was 84 μM Bcl-220–34. Protection with Bcl-220–34also extended to long-term potentiation. No protection was seen with the reverse sequence of Bcl-220–34. Treatment with Bcl-220–34also protected against hypoxic damage, with treated slices recovering to 98% ± 2, while unmedicated slices recovered to 14% ± 2. Similar protection was seen against AMPA, NMDA and nitric oxide. These findings indicate that Bcl-220–34provides specific neuroprotection against acute CA1 neuronal injury.