Sixty-five patients underwent craniotomy for brain tumors; of these 35 had glioblastoma multiforme (GM). The GM cases, as a group, showed significantly higher serum titers for herpesvirus type 1 (HSV-1) neutralizing antibodies (NT) than the non-glioblastoma cases. Both the GM group and the pituitary adenoma group had high levels of HSV-1 serum antibodies with the enzyme-linked immunosorbent assay (ELISA). These data, combined with other evidence, lead us to speculate that HSV-1 infections may be associated with certain brain tumors in humans. However, coincidental causes for these elevated HSV-1 titers must be ruled out.