Quartz crystal microbalances (QCMs) measure mass on the nanogram (ng) scale. We built novel QCMs as toxicity biosensors incorporating living cells. Human endothelial cells or canine macrophages were equilibrated on QCM crystal surfaces until stable oscillation frequencies occurred. Vehicle or sodium azide (NaN 3 ) (25–100mM) was added to these QCMs while continuously collecting crystal oscillation frequency data. At these doses, NaN 3 alters mitochondrial membrane permeability and causes mitochondrial swelling and intrinsic apoptosis. Our studies demonstrated no frequency change in QCMs with untreated cells or without cells but NaN 3 . If NaN 3 was added to either cell type within QCMs, 5 to 8min later increases in oscillation frequency (Δf) occurred (400–1600Hz) that correlated with dose. All frequency changes reverted to baseline by 15min. In parallel, during the first 30min, no change in cell or nuclear areas, or in actin or microtubule distributions, was detected. Yet, mitochondrial size and membrane permeability increased significantly during, but not after, 5 to 8min. Viability studies confirmed dose-dependent toxicity that was predicted and proportionate to the 5- to 8-min Δf. These studies confirm that cell-based QCMs can detect early events in intrinsic apoptosis and reveal unique kinetic information about events occurring within subcellular structures in response to toxins.