Results of in vitro studies carried out by other investigators suggest that insecticide emulsifiers enhance the replication of animal viruses possessing a single-stranded RNA genome. Based on this observation and on epidemiological findings, it has been postulated that insecticide emulsifiers and related compounds may be etiologically involved in Reye's syndrome. Reye's syndrome is an enigmatic pernicious disease of childhood causally associated with an antecedent viral infection, usually influenza, and putatively associated with exposure to environmental chemicals. The present study was carried out to assess the effects of emulsifiers on infection in vivo with influenza type A virus, a virus possessing a single-stranded RNA genome, using the suckling mouse as host, and in vitro using a susceptible line of mammalian cells. Three coded emulsifiers retrospectively identified as Atlox 3409F, Toximul MP8, and Triton X-100 were assayed at concentrations of 1.0, 2.5, 5.0, and 10.0 ppm. None of the emulsifiers enhanced the plaquing efficiency of influenza A/PR/8/34 (HON1) virus in Madin-Darby canine kidney cells (less than a twofold increase), nor did percutaneous application of these emulsifiers at a concentration of 21 parts per thousand in peanut oil enhance the lethality of influenza A/PR/8/34 (HON1) virus infection. Indeed, peanut oil alone, and in combination with the emulsifiers, lowered lethality relative to mice that were treated percutaneously in parallel with physiologic saline.