Large blebs form rapidly on apical membranes of sensory inner hair cells (IHCs) when the organ of Corti is freshly isolated from adult guinea pigs. Bleb formation had two distinguishable phases. Initially, we identified particles labeled with fluorescent annexin V; these rapidly coalesced into larger aggregates. Following particle aggregation, a single membrane bleb emerged from cuticular plate at the vestigial kinocilium location, eventually reaching ~10 µm maximum diameter, blebs this size often detached from IHCs. Development of blebs was associated with elevated concentration of intracellular Na⁺; blocking Na⁺ influx through mechanotransduction and ATP channels in the apical pole of IHCs or by replacement of Na⁺ with N-methyl-D-glucamine prevented Na⁺ loading and bleb formation. Depletion of intracellular ATP, blocking cAMP synthesis, inhibition of vesicular transport with brefeldin A, or inhibition of phosphatidylinositol 3-kinase with LY 294002 each significantly reduced bleb formation in the presence of a Na⁺ load. Neither the mechanism of blebbing, nor the size growth of the IHC blebs, was associated with cellular apoptosis or necrosis. Bleb formation was not significantly reduced, by disassembling microtubules or decreasing intracellular hydrostatic pressure. Moreover, no polymerized actin was observed in the lumen of blebs. We conclude that IHC bleb formation differs from classical blebbing mechanisms and that IHC blebs arise from imbalance of endocytosis and exocytosis in the apical plasma membrane, linked to the Na⁺ loading that occurs in vitro.