The acute toxicity of nitrofurantoin was studied in the young chick deficient in selenium (Se) and/or vitamin E (E). This new and potentially valuable animal model proved to be very sensitive to the toxicity of this nitro drug. The 48-hour LD50 for nitrofurantoin decreased from 148 mg/kg in the Se- and E-supplemented chicks to 53 mg/kg in the Se- and E-deficient chicks. The addition of Se (0.10 ppm as Na2SeO3) alone, but not E (100 IU/kg diet as dl-α-tocopheryl acetate) reduced the toxicity of nitrofurantoin, so that the LD50 for the chicks given Se alone was the same as the LD50 for the E- and Se-fed chicks. Se and E deficiency significantly decreased the Se-dependent glutathione peroxidase and the plasma tocopherol levels. Hepatic glutathione content, hepatic catalase and superoxide dismutase were unchanged by the dietary treatments. However, a toxic dose of nitrofurantoin significantly decreased hepatic glutathione content over time. These data support the concept that the toxicity of this drug may be mediated in part by an oxidative stress generated by the futile reductive metabolism of the parent compound.