Single-photon emission computed tomography (SPECT) with 99mtechnetium-hexamethylpropylamineoxime (HMPAO) noninvasively shows brain perfusion in patients after acute stroke. However, the clinical significance of the increased HMPAO uptake remains unclear. In this study, consecutive patients with hemispheric hemorrhagic and ischemic stroke admitted to the hospital were evaluated prospectively. The increased uptake of HMPAO was determined by visual analysis of SPECT images. The pathogenic mechanism of ischemic stroke was determined using the clinical and computed tomography (CT) criteria including the Toronto Embolic Scale. Of the 500 consecutive patients with acute hemispheric stroke, SPECT was performed in 458 at a mean time 5 +/- 7 days after the onset of symptoms. A strong association was found between SPECT perfusion patterns and pathogenic subtypes of stroke (p < 0.0001). Thus, in 95% of patients with intracerebral hemorrhage the focal absence of perfusion was found, and 26% of lacunar infarctions presented with a normal SPECT appearance. The mean volume of lacunar lesions that did not produce significant abnormalities on SPECT was 2.5 +/- 1.2 ml. Increased HMPAO uptake was associated with a cardioembolic mechanism of stroke: High and mixed perfusion patterns were present subacutely in 29% of patients with cardioembolic stroke, compared to 15% of patients with other types of ischemic stroke (p < or = 0.0006). The increased uptake of HMPAO on SPECT as determined by visual analysis is associated with a cardioembolic mechanism of cerebral ischemia, which could be explained by glutathione-mediated trapping of the tracer during reperfusion and later in newly developed granulation tissue. HMPAO-SPECT may help in early management decisions since it indicates stroke pathogenesis and evolution.