DNA fragmentation and activation of caspase-1, implicating involvement of apoptosis, have been reported in the spinal cord of amyotrophic lateral sclerosis (ALS) patients and transgenic mouse models of ALS. Because BH3-only members of the Bcl-2 family have pro-apoptotic activity, we examined the expression of the BH3-only peptide harakiri (Hrk) in the spinal cord of ALS patients. In situ expression of Hrk mRNA and immunoreactivity against the Hrk peptide were verified in the spinal neurons. In the immunoblot analysis, upregulated Hrk protein migrated at 16 kDa. Heterodimerization of Hrk with Bcl-2 was detected by immunoprecipitation, which suggests the competition of Hrk and anti-apoptotic Bcl-2. These findings suggest that Hrk plays a role in apoptotic events in ALS pathogenesis.