Histamine release from human basophil leukocytes was triggered by Staph. aureus or by complement activation caused by endotoxins isolated from E. coli or Salmonella bacteria. Influenza A virus was found to enhance the mediator release and the effect was caused by synergism, since the virus itself did not release histamine. The potentiating effect of the virus was abolished by a potent neuraminidase inhibitor. Furthermore, a purified neuraminidase preparation obtained from Vibrio cholerae caused a similar potentiating effect, which was also abolished by the neuraminidase inhibitor. These findings indicate that the neuraminidase on the surface of influenza A virus is responsible for the potentiating effect of the virus on basophil histamine release.