In 65 type I diabetic patients we prospectively evaluated brain perfusion by means of single-photon emission tomography after the injection of 740- 1110 MBq of technetium-99m hexamethylpropylene amine oxime. Thirty-five of the patients presented complications secondary to their diabetes. None showed CNS symptoms. A semiquantitative analysis was performed drawing 50 symmetrical regions of interest (ROIs) per patient. The relative contribution of each ROI to the total blood flow in each slice was compared with the relative contribution of the same ROI in a control group of ten healthy volunteers. Relative values of any ROI in the study group higher or lower than the mean +/-2 SD in respect of the same ROI in the control group were considered abnormal. The results revealed hypoperfusion in 207 ROIs in the 65 patients with diabetes mellitus: of these ROIs, 113 were frontal, 10 frontotemporal, 20 temporal, 18 parietal, 11 occipital and 35 cerebellar. A total of 137 ROIs showed hyperperfusion: 17 frontal, 3 frontotemporal, 19 temporal, 18 parietal, 19 parieto-occipital, 29 occipital and 32 cerebellar. Out of 65 type I diabetic patients, 61 showed at least one hypoperfused ROI (P = 0.0064 vs. controls) and 25 showed more than three hypoperfused ROIs. None of the control subjects showed more than three hypoperfused regions (P<0.001). The results obtained demonstrate the existence of subclinical abnormalities of brain blood perfusion in patients with type I diabetes mellitus and no history of cerebrovascular disease, thereby allowing the initiation of intensive preventive measures.