In four patients with thalamic infarcts causing severe neuropsychological deficits, regional cerebral blood flow (rCBF) was measured by single-photon emission computed tomography using (99m)Tc-d,l,-hexamethylpropyleneamine oxime as tracer. In one of these patients, cerebral glucose metabolism was measured by positron emission tomography using (18)F-fluorodeoxyglucose as tracer. Three patients had left paramedian thalamic infarcts, in one case combined with an infarction of the right cerebellar hemisphere, and one had bilateral paramedian and left anterior thalamic infarcts. Neuropsychological assessment revealed profound impairment of memory, verbal fluency, and abstract reasoning, as well as perseveration and varying degrees of dyscalculia and constructional apraxia in all patients. There were distinct personality changes and deficient judgment and insight. All four patients had reduced cortical rCBF in the left frontoparietal regions. In three cases, flow was also reduced in the left temporal lobe; they all presented with a fluent aphasia, which only partly remitted over time. Prosody and mimics were impaired only in the patient with bilateral thalamic infarction. In one of the patients with unilateral thalamic infarct extending into the mesencephalon, glucose metabolism was reduced in the ipsilateral frontal, temporal, and occipital regions. Thalamic infarcts can alter the activity in widespread functional systems of the brain and thus lead to extensive neuropsychological deficits.