Some authors have associated organophosphate compounds with susceptibility to transmissible spongiform encephalopathy (TSE) and even with the origin of this group of diseases. Nevertheless, the actual role played by these compounds still remains unclear. The aim of this study was to assess the effect of oral exposure to dimethoate (DMT) on the development of Scrapie using a genetically modified murine model. A total of 70 C57BL/6 mice over-expressing the PrP gene (Tg20) were included in the present study. A portion of the mice were intraperitoneally inoculated, while the rest were maintained as non-infected controls. Animals from the treated group were exposed to dimethoate dissolved in drinking water from the beginning of the experiment. Variables of incubation period, spongiosis, PrPsc deposits, glial over-expression, neuronal loss, and amyloid plaques were assessed in all animals. According to the results, a treatment consisting of a daily 15 mg/kg dose of DMT for 5 weeks did not show any effect on any of the variables assessed. Although more exhaustive studies for assessing different doses and organic compounds are required, this finding constitutes an empirical study that rules out the possibility that this compound may have a predisposing effect on TSEs.