Induction of interferon by influenza virus was depressed by approximately 50% when mammalian (LLC-MK2) cell monolayers were pretreated with lignite fly ash. The presence of fly ash, however, did not impair the ability of exogenous interferon to confer antiviral cellular resistance. Influenza virus multiplication in cell monolayers pretreated with fly ash attained a twofold higher level of growth than that noted in normal cell monolayers. This was related to suppression of viral interferon induction by fly ash. Whereas aqueous extracts of fly ash had no adverse effect on interferon induction, extractions of fly ash by either polar or nonpolar solvents, by horse serum with or without EDTA (a metal chelator), and fractionation of serum extracts yielded corresponding compounds, most likely organic and inorganic, that were antagonistic to viral interferon induction. Residual fly ash particulates after extraction by horse serum with EDTA were still capable of inhibiting viral induction of interferon. These findings indicate that several soluble components inherent to lignite fly ash and the particulate matrix per se may modify, independently or in concert, cellular defense behavior. Neither polar, nonpolar, nor horse serum extracts of lignite fly ash, however, showed mutagenic activity as determined by the Salmonella histidine reversion assay. Removal of cell-membrane-bound sialic acid (N-acetylneuraminic acid) by neuraminidase or pretreatment of lignite fly ash with sialic acid abolished the adverse activity of fly ash on viral interferon induction. This suggests that the interaction of cell-membrane-bound sialic acid residue with fly ash particulates may be involved in the altered state of cellular behavior described in response to viral induction of interferon.