An experimental approach is described to quantitate inhomogeneity in extracellular K concentration ([K+]out) in the presence of ischemia and to relate this inhomogeneity to the electrophysiologic changes. Extracellular potassium concentration and local direct-current electrograms from the same sites were measured in isolated perfused pig hearts with the use of multiple electrodes. Dispersion of [K+]out is described under three conditions: (1) during regional ischemia in the "central zone" and the "borderzone", (2) during global ischemia, and (3) during perfusion of the heart with a high-K perfusate. Inhomogeneity was greatest during regional ischemia, especially in the borderzone, where generally lower concentrations were measured. When during regional ischemia the normal zone was perfused with a high-K perfusate, dispersion in the ischemic borderzone diminished, and higher concentrations than in the central zone were measured. During global ischemia inhomogeneity was slightly larger than during high-K perfusion. Dispersion during the latter was considered due to experimental error. A decrease in [K+]out during regional ischemia after the initial increase was closely correlated with electrical recovery of the electrograms. This decrease occurred earlier in the borderzone than in the central zone. During ischemia [K+]out was not related to the occurrence of monophasic electrograms, which are indicative of the absence of local regenerative responses. For every single electrode position a linear relationship between TQ depression and [K+]out was found, the slope of which varied with the position of the electrode. When all sites were taken together, there was no correlation between TQ depression and [K+]out. We conclude that: (1) inhomogeneity of K+ is largest in the borderzone, (2) potassium flows from the ischemic zone into the normal zone, (3) transient electrical recovery is related to a decrease (after an initial increase) in [K+]out, which is at least partly due to a flow of K+ toward the normal zone, (4) monophasic ("block") electrograms can be recorded from intrinsically excitable tissue, (5) for every single site in the ischemic region there is a linear relationship between local [K+]out and local TQ segment depression, and (6) the degree of TQ depression at a particular site is not a reliable index of the degree of ischemic injury at that site.