The binding of human lupus anti-DNA antibodies and murine anti-mycobacterial antibodies to human cortical brain tissue sections was assessed by the indirect immunofluorescent technique.Prior adsorption of the reactive monoclonal antibodies on nuclear extracts, ss-DNA, synthetic polynucleotide polymers, histones, mycobacterial glycolipids, and bovine brain extracts abrogated the monoclonal antibodies' binding to the brain. Intermediate blocking activity was conferred also by ribonucleic components as RNP, Ro(SSA), and La(SSB). Specificity to neuronal tissue was demonstrated by failure of non-neuronal tissue extracts to abolish antibodies' reaction to the cortical tissue sections in competition assays. The anti-TB and anti-DNA antibodies seemed to compete on their binding to a common neuronal membranal epitope. These results indicate that mycobacteria share antigens with DNA and human brain tissue.Furthermore, these data support the concept that anti-DNA antibodies may play a pathogenetic role in SLE patients with neuropsychiatric involvement via crossing of a“leaky”blood brain barrier and attachment to brain tissue components.