High mobility group 1 (HMG1) is a 26kD highly con- served non-sequence-specific DNA-binding nuclear protein. Mammalian HMG1 has two homolo-gous DNA- binding domains HMG boxes, A and B (each of 80–90 amino-acid residues), linked by a short basic region to an acidic C-terminal domain containing 30 consecutive Asp and Glu residues. HMG1 has been implicated in a number of fundamental biological processes including transcription, replication and recombination, in which it plays a role in manipulating DNA structure by bending, looping, compaction or unwinding, or by direct contacts with distinct cellular proteins. HMG1 can act as a repressor, by interacting with TBP to block pre-initiation complex formation or as an activator, by facilitating the binding of various transcription factors to their cognate DNA sequences. Most recently, it was discovered that HMG1 is a late mediator of delayed endotoxin lethality by activating downstream cytokine release.