We investigated regional cerebral blood flow (rCBF) using the [99mTc]-d,l-HMPAO technique with brain dedicated high resolution single photon emission computer tomography (SPECT) in 14 consecutive patients with amyotrophic lateral sclerosis (ALS), median age 62 years (45-77). Global CBF, expressed in % relative to the cerebellum, was significantly lower (P less than 0.05) in the ALS group (80.5 +/- 6.7%) than in the control group of 14 age-matched healthy volunteers (87.0 +/- 7.5%). Eight patients (57%) had abnormal rCBF distribution maps with reduced flow, primarily in the frontal lobes. Three of the 8 patients with abnormal rCBF had mild to moderate dementia and another one had mild aphasia. None of the patients with normal rCBF distribution maps had dementia. In the group of ALS patients as a whole rCBF was significantly reduced in the frontal cortex, the hippocampus, and the central white matter. We conclude that reduced rCBF, primarily in the frontal lobes, is a frequent finding in patients with ALS. The decreased rCBF may be associated with cognitive deficits and is most likely caused by neuronal degeneration and reduced metabolic needs.