The purpose of this study was to investigate patterns of 99mTc-HMPAO single-photon emission computed tomography (SPECT) abnormality in Lewy body disease (LBD) and to compare findings with those encountered in Alzheimer's disease (AD). The study group comprised 20 consecutive patient referrals fulfilling clinical criteria for LBD. All patients had fluctuating cognitive impairment and 'subcortical' dysfunction with or without perceptuospatial and/or linguistic impairment. Six patients had asymmetrical signs of parkinsonism (three left-sided and three right-sided), and 14 patients had symmetrical features of extrapyramidal involvement. 99mTc-HMPAO SPECT imaging was performed on LBD patients and findings compared with those of 57 patients with 'probable' AD and 11 normal age-matched controls. Within the LBD and AD groups, patterns of cortical and subcortical blood-flow abnormality were compared with patterns of cognitive and neurological breakdown. LBD was associated with bilateral posterior cortical blood flow abnormality, a pattern strikingly similar to that found in AD. Within the LBD group, cortical blood-flow abnormality was found to reflect patterns of neurological dysfunction (parkinsonism) indicative of subcortical involvement. In contrast, cortical blood-flow changes did not reflect patterns of neuropsychological impairment suggestive of cortical dysfunction. Within the AD group, cortical blood-flow changes were mirrored by the pattern of neuropsychological impairment. Findings support the notion that cortical blood-flow abnormality in LBD might reflect a combination of direct cortical pathology and cortical deafferentation secondary to subcortical Lewy body pathology. It would appear that 99mTc-HMPAO SPECT imaging is of limited value in the clinical differentiation of LBD and AD.