The study was performed to investigate subclinical abnormalities in regional cerebral blood flow (rCBF) in patients with insulin-dependent diabetes mellitus (IDDM) and to correlate them with patients characteristics. After intravenous injection of technetium-99m hexamethylpropylene amine oxime (HMPAO), tracer uptake of the prefrontal, frontal and parieto-occipital zones was measured with a triple-head single-photon emission tomography (SPET) camera system in 35 IDDM patients outside an episode of hypoglycaemia. Tracer uptake values in 16 age- and sex-matched healthy volunteers served as reference values. Compared with healthy subjects, increased tracer uptake of both prefrontal regions and the left frontal region could be shown in diabetes. Tracer uptake was negatively correlated with the duration of diabetes in all investigated regions. In diabetic patients with a disease duration of more than 5 years (n=26), stepwise regression analysis revealed a significant positive correlation between their HbA1c levels and tracer uptake. Long-term diabetic patients with reduced (pre)frontal tracer uptake (n=8) had lower HbA1c levels than those without (8.4%+/-0.2% vs 9.3%+/-0.3%, P<0.05) and tended to have more frequently a history of hypoglycaemic coma (6/8 vs 6/18, P=0.06). It can be concluded that duration of diabetes contributes to subclinical changes in basal rCBF in IDDM as detected with HMPAO SPET of the brain. The positive correlation between the presence of regional hypoperfusion and lower HbA1c levels in long-term diabetic patients may be interpreted in the light of a presumed higher incidence of hypoglycaemia as metabolic control improves.