HS1-associated protein X-1 (HAX-1) and presenilin-associated rhomboid-like protein (PALR) were reported to play an important role in the activation of HtrA2/Omi, which is also designated PARK13, in the mitochondria. To elucidate the role of HAX-1 and PARL in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB), we performed immunohistochemical studies on HtrA2/Omi, HAX-1 and PARL using autopsied brains from 8 normal subjects, 10 patients with PD and 5 patients with DLB. In accordance with our previous report, brainstem-type and cortical Lewy bodies were strongly immunopositive for HtrA2/Omi. In the normal brains, HAX-1 and PARL immunoreactivities were observed in various types of neurons in the cerebral cortex, midbrain, and upper pons. HAX-1 and PARL immunoreactivities were also observed in the remaining neurons, and brainstem-type and cortical Lewy bodies were intensely immunoreactive for HAX-1 and PARL. Both immunoreactivities were localized to the halo or core of brainstem-type Lewy bodies. Our results suggest that brainstem-type and cortical Lewy bodies may contain HAX-1 and PARL as well as HtrA2/Omi, and that these proteins may partially contribute to the formation of Lewy bodies and may be associated with the pathogenesis of PD and DLB.