Using dot blotting, we found Epstein-Barr virus genome in three AIDS-related primary cerebral lymphomas (PCLs), but in none of 39 sporadic PCLs. Human herpesvirus-6 sequences were present only in one sporadic PCL, as revealed by polymerase chain reaction and Southern analysis. We conclude that these viruses do not appear to play a major role in PCL pathogenesis in immunocompetent subjects.