The nucleus is surrounded by a double membrane separating it from the cytoplasm. The perinuclear space is continuous with endoplasmic reticulum, and the nuclear outer membrane shares many features with the reticular membrane. We now show that inositol 1,4,5-trisphosphate (InsP3) receptors associated with the nucleus release Ca2+ from isolated Xenopus laevis oocyte nuclei. Electrophysiological measurements of the intracellular InsP3 receptor in its native membrane have not been possible on the fine filamentous endoplasmic reticulum. In this paper, we directly measure InsP3-dependent receptor channels in isolated nuclei. The nuclear InsP3 receptor is activated by InsP3 and modulated by Ca2+. The channel is weakly regulated by ATP, is mildly voltage dependent, and has a greater conductance with monovalent cations than with divalent cations.