To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I-IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.