1. Native Xenopus oocytes were voltage clamped and exposed to Ringer solutions containing low concentrations of divalent cations. Oocytes, held at -60 mV, developed a reversible non-inactivating smooth inward current (Ic) associated with an increase in membrane conductance. 2. Ic was selectively carried by cations (Na+, K+), indicating that the current was not the result of a non-specific membrane breakdown, but was due instead to removal of a blocking effect of divalent cations on a specific population of endogenous ionic channels located in the oocyte membrane. 3. The blocking effects of Ca2+ and Mg2+ were voltage dependent, implying action at a binding site within the pore of the cationic channel. For example, the half-maximal inhibition (IC50) of Ic by Ca2+ was 61 microM in oocytes held at -60 mV and 212 microM in oocytes held at 0 mV. 4. The Ic channels could be unblocked by depolarization of the membrane even in the presence of physiological concentrations of Ca2+ or Mg2+. The unblocking of the channels was observed as a slowly developing outward current. 5. The novel cationic current was substantially reduced following in vitro maturation of oocytes by treatment with progesterone (10 microM, 4-5 h). 6. The physiological role of Ic channels remains to be elucidated. Nonetheless, their characteristics explain the ionic basis of the sensitivity of oocytes to reductions in extracellular divalent cations and raise the possibility that the channels play a role in calcium homeostasis.