The ultimate concern over pesticides in the environment is their toxic impact on nontarget organisms, including humans. Soil clays are known to interact with pesticides in ways that decrease the concentration of the parent compound in the soil solution (adsorption, sequestration, degradation). These phenomena are generally regarded as beneficial, but toxicological verification is lacking. In this study, mammalian-cell cytotoxicity of four commonly used agricultural chemicals (2,4-D, alachlor, dicamba, and oxamyl) was assessed after exposure to either reduced or oxidized ferruginous smectite (SWa-1). Results revealed that treatment with reduced smectite produced differential effects on mammalian-cell viability, depending on the pesticide. Oxamyl and alachlor reacted with reduced SWa-1 showed a significant decrease in their overall cytotoxic potential. Dicamba reacted with the reduced-clay treatment and generated products that were more toxic than the parent pesticide. Finally, no differences were observed between redox treatments for 2,4-D. The significance of these results is that oxidized smectites have virtually no influence on the toxicity of pesticides, whereas reduced-Fe smectite plays an important role in altering the cytotoxic potential of agricultural pesticides. The Fe oxidation state of clay minerals should, therefore, be taken into account in pesticide management programs.