Inducible heat shock protein 70 (HSP70), a stress protein detected in the central nervous system, is expressed when a cell or organism is under stress. Interleukin-18 (IL-18) and tumor necrosis factor alpha (TNF-alpha) are multipotential early proinflammatory cytokines. Our objective was to determine protein levels of HSP70, IL-18, and TNF-alpha as well as mRNA levels of HSP70, IL-18, and TNF-alpha in the plasma and CSF of spontaneous intracerebral hemorrhage (ICH) patients, and to correlate these with disease outcome. Serial measurement of the proteins in CSF and plasma and of the mRNAs in peripheral blood mononuclear cells was conducted in 43 patients (mean age, 64+/-9 years; 23 men and 20 women). Ten (23%) patients died. We found that the damaged brain releases TNF-alpha and HSP70 to the peripheral blood and that plasma levels of these are highly associated with mortality in spontaneous ICH patients.