Acute, progressive global brain ischemia was induced in awake or anesthetized rats for 5-75 min. Ischemia was achieved with a subclavian-carotid artery occlusion technique (SCOT). After thoracotomy, both subclavian arteries (proximal to their vertebral branches) were tied-off and carotid artery catheter-snares installed. Results show progressive morphological, physiological and neurochemical damage when CBF was reduced from preischemic levels of 115 ml to 0 blood flow. 31P magnetic resonance spectroscopy of high energy phosphate metabolites in vivo showed loss of PCr and beta-ATP signals after 6 min brain ischemia. Energy metabolite levels, EEG and CBF normalized within hours after reperfusion. Degree of neuropathologic damage to hippocampal region appeared linearly related to the ischemic duration of ischemia. Thus, acute global brain ischemia resulted in loss of high energy phosphate metabolites, EEG and neuronal integrity in the hippocampal subfields. Reperfusion following short (5 min) or long (75 min) periods of global brain ischemia induced return of 31P-spectra, EEG and CBF to normal but was unable to reverse all of the neuronal damage at the end of the 72-h observation period.