We have investigated the characteristics of binding of the organophosphorus insecticides methyl parathion and chlorpyrifos to DNA. Quantitative analysis of our data indicates that if these compounds bind to DNA at all, it is only with weak affinity. Dissociation constants would, according to our analysis, be in excess of 1 mM. Concentrations of methyl parathion and chlorpyrifos in this range are considerably greater that those expected to occur in organisms exposed to sub-lethal amounts of the compounds. Furthermore, the compounds methyl paraoxon and chlorpyrifos oxon, which result from biotransformation of methyl parathion and chlorpyrifos, exhibit similar characteristics (i.e., bind not at all or with weak affinity). These data suggest that direct binding of methyl parathion and chlorpyrifos to DNA is unlikely to be a mechanism through which any genotoxic effects are produced.