The contribution of extracranial tissue damage to serum S100beta increases was examined in 18 marathon runners without clinical or laboratory signs of brain damage. Postrace serum S100beta and creatine kinase (CK) concentrations increased (p < 0.001), and areas under the curve were highly correlated (p = 0.001). To conclude, serum S100beta increases after running originate from extracranial sources. CK determination may improve specificity of S100beta as a marker of brain tissue damage in acute trauma.