Antineutrophil antibodies were detected in the serum of 12 of 14 patients with acute Epstein-Barr virus-induced infectious mononucleosis. These antibodies were present in two patients with mononucleosis and severe neutropenia, and in 10 patients with mononucleosis uncomplicated by severe neutropenia. Antineutrophil antibodies were not detected in serum from five patients with cytomegalovirus-induced mononucleosis, or five renal allograft recipients with primary or reactivation Epstein-Barr virus infection. This study suggests that antineutrophil antibodies are among those produced by the polyclonal activation induced by Epstein-Barr virus during acute infectious mononucleosis.