A short duration of ischemia (i.e., ischemic preconditioning) was shown to result in significant tolerance to subsequent ischemic injury. Since previous reports suggest that interleukin-1 (IL-1) may be involved in both ischemic damage and neuroprotection, the present work examined the expression of IL-1 mRNA in cortical brain tissue after an established preconditioning (PC) stimulus known to produce significant brain tolerance to focal stroke after 1-7 days. Significant induction of IL-1 mRNA was observed in the ipsilateral cortex at 6 hr (87 Ϯ 9 copies of the mRNA per microgram of brain tissue compared to 16 Ϯ 5 copies in sham-operated samples, P Ͻ 0.001, n ϭ 4) and 8 hr (46 Ϯ 4 copies, P Ͻ 0.01, n ϭ 4) after PC by means of real-time Taqman polymerase chain reaction (PCR). The peak expression of IL-1 mRNA after PC was significantly (P Ͻ 0.01) lower than that after permanent occlusion of the middle cerebral artery (MCAO), i.e., 87 Ϯ 9 and 546 Ϯ 92 copies of RNA per microgram tissue at peak levels for PC and focal stroke, respectively. Immunohistochemistry studies revealed a parallel induction of IL-1 in the ipsilateral cortex after PC. The maximal expression of IL-1 was observed during the first week post-PC, showing marked parallelism with the duration of ischemic tolerance. These data suggest that the significant but low levels of IL-1 induction after PC may contribute to ischemic brain tolerance.