We analyzed the potential use of the lipophilic chelate complex thallium diethyldithiocarbamate, TlDDC, for delineation of ischemic injury in rats in hyperacute and late stages in a rat MCAO model of focal cerebral ischemia. We systemically injected TlDDC 15 minutes and 7 days after medial cerebral artery occlusion and used a recently developed histochemical technique, Tl+ autometallography, for non-radioactive high- resolution mapping of the Tl+ distribution in the brain. The Tl+ distribution indicates that Tl+ is released from the complex into the brain extracellular space and taken up by neurons and glial cells in an activity-dependent manner. Since Tl+ is a K+-probe the images we show provide insight into brain K+ metabolism in hyperacute and late stages of cerebral ischemia. In the hyperacute phase we find a core region where Tl+-uptake is dramatically reduced in neurons while astrocytes still take up the tracer. In the region surrounding the core astrocytes are intensely stained while in neurons both decreases and increases in Tl+-content can be observed. In the late stage glial uptake is markedly increased. We suggest the use of TlDDC for imaging brain potassium metabolism and tissue viability in animals and humans.