The effect of four azo dyes, Congo-Red (573580), trypan-blue (72571), benzopurpurine-4B (992596), and Direct-Blue-15 (2429745), and their derivatives, benzidine (92875), o-tolidine (119937), and o- dianisidine (119904) on viral interferon induction, following enzymatic dye activation by rat liver S9 fraction, was tested in Rhesus-monkey kidney cell monolayers. The agents were added to cell cultures in four different concentrations and incubated for 24 hours, followed by interferon induction by influenza-virus. Three of the four azo dyes tested inhibited the induction of viral interferon by 35 to 60 percent, while trypan-blue and the azo dye derivatives induced negligible inhibition. All chemicals tested caused significant inhibition of interferon induction when rat S9 was used for enzymatic activation. Uninduced hamster liver S9 fraction and Aroclor-1254 induced hamster and rat liver S9 fractions demonstrated comparable metabolic activation of the agents tested. Inhibition of interferon induction was related to the dose of the compound. S9 fractions also showed dose related activity, and concentrations higher than 0.5 percent inhibited interferon induction. The author concludes that potential mutagens and carcinogens which require metabolic activation may be identified according to their ability to inhibit the induction of interferon in mammalian cell cultures.