Cerebral perfusion measurements with(99m)Tc-hexamethylpropyleneamine oxime single photon emission computed tomography (HMPAO SPECT) are potentially clinically useful in the investigation of patients with acute ischaemic stroke. The normal side-to-side asymmetry on(99m)Tc-HMPAO SPECT images may be greater in the stroke-age population than in younger age groups. To assess the extent of variation we studied 66 volunteers with(99m)Tc-HMPAO SPECT who were closely age matched to a stroke population and who had normal CT and extracranial and intracranial vascular ultrasonography. By measuring the side-to-side ratios in 19 regions of interest, the normal side-to-side perfusion asymmetry was determined and, as a secondary aim, variations in regional asymmetry were correlated with age. After repeated measurement analysis of variance (ANOVA), the normal range of side-to-side ratios in this population was 1.003+/-0.145 (mean+/-1.96 SD, ANOVA). The two regions with the greatest side-to-side asymmetry values were (1) the superior lateral temporal cortex (higher on the right relative to the left) and (2) the superior parietal cortex (higher on the left relative to the right). The orbitofrontal and posterior temporal cortices demonstrated significantly increased bidirectional variation with age (P< 0.05). In a stroke-age population hemispheric perfusion is relatively symmetrical and a side-to-side variation of greater than +/-14.5% may be defined as pathological. This value is higher than that reported in younger volunteers suggesting that there is a mild increase in the side-to-side perfusion asymmetry with age. Increased variation in the orbitofrontal and posterior temporal cortices occurs with age and should be borne in mind when interpreting HMPAO SPECT studies. Copyright 1999 Harcourt Publishers Ltd.