Electrophysiological effects of anaphylactic stimulation of rat basophilic leukemia cells (RBL-2H3) were studied using conventional microelectrodes. Stimulation of passively sensitized cells by anti-immunoglobulin E resulted in hyperpolarization followed by depolarization. These changes in membrane polarization were associated with a decrease in input membrane resistance. No effect of anaphylactic stimulation was seen in Ca2+-free solution or when Ca2+ influx was blocked by Co2+, but it was mimicked by the Ca2+ ionophore A-23187. This suggests that the changes in ionic conductances were associated with calcium influx. These results support the hypothesis that membrane conductance changes are involved in the stimulus-secretion process of the RBL-2H3 cells.