Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) play crucial roles in host innate immune response against microbial infections. These receptors share a conserved cytoplasmic domain, the Toll/interleukin-1 receptor (TIR) domain, which is required for signaling through these receptors. Structural information on the TIR domains will be essential for understanding the molecular basis for signal transduction by these receptors.