A patient with HBsAg-positive chronic aggressive hepatitis and HBeAg and hepatitis B virus DNA (HBV DNA) developed fatal Creutzfeldt-Jakob disease. The investigation of cerebrospinal fluid and a temporal lobe brain tissue post mortem sample with radioactive probes of previously cloned HBV DNA showed the unquestionable presence of viral nucleotide sequences in the nervous tissue (about 9 viral genomes per cell). Although a pathogenetic role in the underlying neurologic disease cannot be attributed to HBV, our observation widens the spectrum of tissues where HBV has been detected, and supports the contention that there are replicative extrahepatic foci where the immunologic system of the host is permissive for the virus.