Tc-99m hexamethylpropylene amineoxime (HMPAO) brain perfusion SPECT was correlated with CT, MRI, and clinical findings in 17 patients with acute and subacute aphasia to determine its diagnostic potential in the early phases of stroke-associated language dysfunction. SPECT was performed using a dedicated brain imaging system after intravenous injection of 20 mCI (740 MBq) of Tc-99m HMPAO. Transaxial and three-dimensional surface rendered images were evaluated visually, and perfusion defects were correlated with CT, MRI, and a standard battery of clinical tests for aphasia. Clinical examination was insufficient for anatomic localization of aphasia in more than 40% of patients. CT exams were normal in 5 patients, although SPECT demonstrated perfusion defects in all 17. Nonfluent aphasia was present in only 6 of 10 patients with perfusion defects in Broca's area and fluent aphasia was present in only 5 of 10 patients with lesions in Wernicke's area. Auditory comprehension defect was associated with perfusion defects in the inferior parietal region in 9 of 12 patients (P = 0.05); reading and writing abnormalities were associated with perfusion defects in the posterior frontal, superior and inferior parietal cortex, and superior temporal gyri, and repetition deficit was associated with defects involving the inferior parietal cortex, the supramarginal and angular gyri, and the ipsilateral thalamus in 8 of 11 patients (P < 0.05). Brain perfusion SPECT should be included in the initial evaluation of aphasic patients, because clinical tests of aphasia and morphological imaging have limited value for accurately determining the extent and location of functional deficits.