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Two brain-specific proteins, S-100β and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100β levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100β is a marker of blood–brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100β increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100β is an early marker of BBB opening that is not necessarily related to neuronal damage.