The modulating effects of tannic acid (TA) on somatic mutation and mitotic recombination induced by methylmethanesulfonate (MMS), nitrogen mustard (HN2), and mitomycin C (MMC) were evaluated in the standard (ST) cross of the wing spot test in Drosophila melanogaster using co- and posttreatment protocols. It was shown that TA alone did not modify the spontaneous frequencies of single and twin spots, which means that this polyphenol neither acts as a genotoxin nor exerts any antigenotoxic effect over spontaneous DNA lesions. However, the simultaneous administration of genotoxins with TA can lead to considerable alterations of the frequencies of induced wing spots in comparison to those with administration of the genotoxins alone. In fact, TA produced a significant increase in HN2-induced wing spots with enhancements between 90 and 160%. For MMS, the enhancement was 38% in the highest TA concentration tested. In contrast, a significant protective action of this polyphenol was observed in combined treatments with MMC (64 to 99% inhibition). Moreover, the data from TA posttreatments demonstrated that this agent is not effective in exerting protective or enhancing effects on the genotoxicity of MMS, HN2, or MMC. One feasible mechanism of TA action is its interaction with the enzyme systems catalyzing the metabolic detoxification of MMS and HN2, which may also be involved in the bioactivation of MMC.