Long-lasting spike activation of CA3 hippocampal pyramidal neurons is shown to cause the development of a large and long-lasting (greater than 50 s) membrane hyperpolarization (PTH). Under normal conditions this PTH is mainly given by a relatively potential-independent process, presumably an electrogenic sodium pump. Following reduction in pump activity (cooling, ouabain), the PTH remains but is mainly produced by a conductance process, presumably a K conductance increase resulting from a sodium-induced calcium release from intracellular stores.