The intermediate conductance Ca2⁢-activated K⁢ channels (SK4, IKCa1) are present in lymphocytes, and their membrane expression is upregulated by various immunological stimuli. In this study, the activity of SK4 was compared between Bal-17 and WEHI-231 cell lines which represent mature and immature stages of murine B lymphocytes, respectively. The whole-cell patch clamp with high-Ca2⁢ (0.8μM) KCl pipette solution revealed a voltage-independent K⁢ current that was blocked by clotrimazole (1 mM), an SK4 blocker. The expression of mRNAs for SK4 was confirmed in both Bal-17 and WEHI-231 cells. The density of clotrimazole-sensitive SK4 current was significantly larger in Bal-17 than WEHI-231 cells (⁣11.4⁑3.1 Vs. ⁣5.7⁑1.15 pA/pF). Also, the chronic stimulation of B cell receptors (BCR) by BCR-ligation (anti-IgM Ab, 3μg/ml, 8∼12 h) significantly upregulated the amplitude of clotrimazole- sensitive current from ⁣11.4⁑3.1 to ⁣53.1⁑8.6 pA/pF in Bal-17 cells. In WEHI-231 cells, the effect of BCR-ligation was significantly small (⁣5.7⁑1.15 to ⁣9.0⁑1.00 pA/pF). The differential expression and regulation by BCR-ligation might reflect functional changes in the maturation of B lymphocytes.