In the present study, the number of neurons (greater than 20 microns in diameter) within the lateral part of the pedunculopontine nucleus pars compacta (PPNc) was determined at six rostrocaudal levels in 3 subjects with progressive supranuclear palsy (PSP), in 9 subjects with Alzheimer's disease, and in 6 age-matched control subjects. At each level examined, significantly fewer neurons were present in patients with PSP than in control subjects (49 to 69% reduction). Significant differences in numbers of neurons were not demonstrated between control subjects and patients with Alzheimer's disease. The extent of pathological changes, particularly neurofibrillary tangles, was examined within the PPNc of subjects in these three groups. The average number of neurofibrillary tangles in a 12-microns-thick midlevel section of the lateral PPNc was 68.7 in subjects with PSP, 18.3 in those with Alzheimer's disease, and 3.0 in aged control subjects. These abnormalities of PPNc neurons in PSP may play important roles in some of the clinical features characteristic of this disease.