Biochemical markers for the major neurotransmitter systems were measured in the brains of 5 patients who had died with neuropathologically confirmed progressive supranuclear palsy. A marked nigrostriatal dopamine deficiency, observed in 4 of the 5 patients, was sufficient to explain the parkinsonian features (especially bradykinesia) observed in patients with progressive supranuclear palsy. Dopamine concentrations, however, were normal in the nucleus accumbens, hypothalamus, and temporal cortex. Brain noradrenalin, serotonin, gamma-aminobutyric acid, and aspartic acid levels were generally normal. Normal brain choline acetyltransferase activity (the marker enzyme for cholinergic neurons) in the 2 patients with severe dementia suggests that, at least in some patients, the cognitive impairment in this disorder is likely to be related to noncholinergic neurotransmitter system changes. The glutamic acid concentration was elevated in many brain areas in 3 of the 5 patients studied.