Hippocampal slices are generally treated as equivalent regardless of their site of origin along the septotemporal axis. In this study, spontaneous epileptiform bursting was induced in area CA3 of rat hippocampal slices by bathing them in 7 mM potassium. The frequency of spontaneous bursting was measured in all viable slices from 12 hippocampi. Burst frequency was found to vary markedly and in a consistent fashion with site of slice origin along the septotemporal axis. Burst frequency was maximal in slices from near the temporal end and declined progressively toward the septal end. This finding was independent of slicing angle. These results demonstrate that site of slice origin along the septotemporal axis is an important confounding variable in in vitro studies of hippocampal neuronal activity. Furthermore, they support the notion that the temporal portion of the hippocampus may be more prone to seizure activity than the septal hippocampus, possibly because of factors intrinsic to the hippocampus.