Regional cerebral blood flow (rCBF) was measured using N-isopropyl-123I-iodoamphetamine (123I-IMP) with single photon emission computed tomography (SPECT) in 27 patients with diabetes mellitus with an average age of 64.1 years and with an average fasting plasma glucose of 145 mg dl-1. Their data were compared with those of 12 non-diabetic subjects with an average age of 64.6 years. None had cerebral infarction on computed tomographic (CT) studies. There were no significant differences in the physiological or laboratory data between the diabetic and non-diabetic groups except for their fasting plasma glucose and HbA1c levels. A reference sampling method using continuous arterial blood sampling was employed to quantify the rCBF. The average rCBF in each region of the cerebrum and cerebellum was significantly lower in the diabetic group than in the non-diabetic group (P < 0.01). Although a definite cause was obscure, the rCBF of the diabetic patients was reduced even in the absence of findings indicative of cerebral infarction on a CT study.