We used immunohistochemical analysis to determine whether medulla oblongata neurons containing phenylethanolamine N-methyltransferase (PNMT) are affected in patients who died with idiopathic Parkinson's disease (n = 7) compared with age-matched control subjects who died with nonneurological diseases (n = 8). Transverse sections (50 microns) of medulla were prepared either for conventional neuropathological examination or for the immunohistochemical demonstration of PNMT. Immunopositive neurons at approximately 30 rostrocaudal levels, evenly spaced throughout the whole medulla, were mapped and cells in each section were counted with a camera lucida system linked to a computer. In the ventrolateral medulla, from the level of the obex to 11 mm rostral to the obex where the C1 group of neurons is located, there were 7,631 +/- 844 PNMT-positive neurons in control brains and 3,604 +/- 1,051 in brains affected by Parkinson's disease (47% of control). Many PNMT-positive neurons contained Lewy bodies. We observed a previously undescribed midline (C3) group of PNMT-positive neurons in normal brains, and this group was also severely affected (12% of control) in parkinsonian brains. Neither the C2 group nor the small PNMT-positive neurons in the nucleus tractus solitarii were significantly reduced in numbers but there was a reduction in the numbers of melanin-pigmented cells in both the ventrolateral (50% of control) and the dorsomedial (79% of control) region. Our results demonstrate a selective loss of C1 and C3 PNMT-positive neurons, providing the first quantitative evidence for damage to these presumed brainstem sympathetic premotor neurons in Parkinson's disease. These changes may underlie some of the autonomic symptoms occurring in this condition.