To characterize the distribution of transcription factor AP-1 and YY1 DNA-binding activities in the rat brain, the labeled target oligonucleotides were loaded on brain sections and after incubation and washing, the residual signal was registered by autoradiography. The binding was predominantly associated with neurons and was regionally specific with highest levels in the cerebellum, hippocampus, and piriform cortex. The identified binding factor was not, however, sequence-specific, but apparently recognized DNA ends and was activated by long double-stranded DNA. UV cross-linking identified the molecular mass of the factor to be about 80 kDa. The factor was not found in soluble brain extracts, suggesting its association with membranes or the nuclear matrix. Despite apparent similarities with Ku protein, which targets DNA-ends, the DNA end-binding activity was present in brains of Ku86- and Ku70-deficient mice. Since DNA end-binding factors are generally involved in DNA repair, the same function may be suggested for the novel factor identified in the present study.