The inhibition of viral interferon induction by metabolites of benzo(a)pyrene (50328) (BaP) was investigated. The studies utilized the Ao/PR/8/34-influenza and Sendai-parainfluenza virus strains incubated with Rhesus-monkey kidney and human Chang conjunctival cell lines. The BaP metabolites included phenols, quinones, diols, diol epoxides, tetrols, triols, and 6-substituted derivatives and were assayed with and without rat liver S9 activation. Interferon was assayed by adding treated cell supernatants, which had been filtered, to cell monolayers challenged with Sendai virus; the infected cells were examined by direct fluorescent antibody staining. Pretreatment of the cell monolayers with BaP had no effect on the viral induction of interferon. The phenol, diols, and 6- substituted BaP derivatives showed significant inhibition of viral interferon induction in the presence of S9 activation only. The BaP diol epoxides, but not their tetrol and triol derivatives, directly inhibited viral interferon induction in the cell lines tested. Quinone metabolites had little effect on interferon induction, although S9 activation caused a slight increase in inhibition. The relationship of the results to the reported microbial mutagenicities of the respective BaP metabolites was discussed. The authors conclude that the effects of BaP metabolites on virus mediated interferon induction extends the existing assay methods for identifying biologically reactive mutagenic carcinogens.