The effects of short-duration forebrain ischemia on cerebral metabolism in the rat have been studied using several nuclear magnetic resonance (NMR) techniques. In vivo phosphorus-31 (31P) NMR spectroscopy showed that the model produces rapid cerebral energy failure and acidosis. Reperfusion was accompanied by recovery of high-energy metabolites in about 30 minutes, with a slower recovery of pH. Proton (1H) NMR spectra of perchloric acid extracts of selected brain regions showed that levels of alanine and gamma-aminobutyric acid (GABA) were elevated and the level of glutamate was depressed immediately after the ischemic insult, returning to normal by 24 hours. The lactate level remained elevated for up to 7 days after ischemia, suggesting ongoing abnormal mitochondrial function. Postischemic cerebral glucose metabolism was monitored using carbon-13 (13C)-labelled glucose as an NMR probe. Glycolysis was impaired immediately after the ischemic insult, resulting in accumulation of glucose in the tissue and reduced formation of amino acids and tricarboxylic acid cycle intermediates. Glycolysis recovered by 1 hour, but underwent a secondary decrease at 24 hours, the time at which neuronal injury became manifest histologically and physiologically. Nuclear magnetic resonance imaging was used to follow the regional development of tissue injury in selectively vulnerable brain regions. Striatal changes were evident by 24 hours after reperfusion, increasing in intensity and accompanied by hippocampal changes by 48 hours, then becoming less pronounced by 72 hours. Histologic analysis of regional neuronal injury correlated well with the imaging results, establishing NMR imaging as a noninvasive method of visualizing the regional development of ischemic tissue injury.