Abstract BH4 domain is critical for the anti-apoptotic functions of Bcl-2 and Bcl-x L and their binding abilities with other members of the Bcl-2 family. The cleavage of the BH4 domain in Bcl-x L and Bcl-2 by caspase 1 or 3 converts the anti-apoptotic Bcl-x L and Bcl-2 into pro-apoptotic proteins that potently induce apoptosis. Herein, we report that recombinant Bcl-x L proteins without N-terminal 61 residues, His 6-NΔ61-Bcl-x L-CΔ21 and NΔ61-Bcl-x L-CΔ21, form oligomers in solution, whereas Bcl-x L-CΔ21 exists as a monomer. The oligomerization of the truncated proteins is independent of protein–lipid interaction, protein concentration or the ion strength of the solution. Circular dichroism spectrum shows a significant decrease in the content of α-helices upon deletion of N-terminal residues. NΔ61-Bcl-x L-CΔ21 also loses its heterodimerization capability with the BH3 peptide derived from Bak. This newly acquired property might be linked to its ability to induce apoptosis in cells.