The depletion of intracellular calcium stores by thapsigargin treatment evoked extracellular calcium-dependent membrane currents in Xenopus laevis oocytes. These currents have been compared to those evoked by microinjection of a calcium influx factor (CIF purified from Jurkat T lymphocytes. The membrane currents elicited by thapsigargin treatment (peak current, 163 ± 60 nA) or CIF injection (peak current, 897 ± 188 nA) were both dependent on calcium entry, based on their eradication by the removal of extracellular calcium. The currents were, in both cases, attributed primarily to well-characterized Ca^(2+)-dependent Cl^- currents, based on their similar reversal potentials (-24 mV vs. -28 mV) and their inhibition by niflumic acid (a Cl^- channel blocker). Currents induced by either thapsigargin treatment or CIF injection enhibited an identical pattern of inhibitory sensitivity to a panel of lanthanides, suggesting that thapsigargin treatment or CIF injection evoked Cl^- currents by stimulating calcium influx through pharmacologically identical calcium channels. These results indicate that CIF acts on the same calcium entry pathway activated by the depletion of calcium stores and most lanthanides are novel pharmacological tools for the study of calcium entry in Xenopus oocytes.