In rat hippocampal tissue slices we recorded extracellular potential (Vo) and whole-cell patch clamp current of CA1 pyramid cells. During hypoxic spreading depression (SD)-like depolarization, the holding current (Ih) increased sharply. Membrane 'slope' resistance (Rm) decreased to 10-67% (mean 39%) of the resting value. The SD-related membrane current (ISD) reversed near zero mV. With voltage dependent K+ and Na+ currents blocked by Cs+ and QX-314, shifts of Ih and decrease of Rm during SD were not suppressed. We conclude that hypoxic SD of CA1 pyramidal cells is associated with a large non-selective inward current through yet to be identified membrane mechanisms, which cannot fully explain the SD-related Vo shift.