Although selenium or vitamin E deficiencies or changing from cereal-based to purified diets augments paraquat toxicity, the action of other dietary components in normal animals fed nutritionally adequate diets is not clear. Upon injection of mice with antiinflammatory agents, a protective action of the corn oil vehicle against paraquat lethalities was noted. This preventive action of a large parenteral administration of unknown components in oils served as the basis for this study. Intramuscular injection of various vegetable oils protected similarly, indicating that in mixtures, the degree of lipid saturation did not seem to be an important factor. Injection of the monounsaturated fatty acid oleic acid decreased oral paraquat lethalities in mice, but linoleic, gamma-linoleic or linolenic acids were not protective in either male or female mice. Measurement of paraquat concentrations in various tissues at various times after administration indicated no effect of corn oil on paraquat distribution. Although the exact mechanism of the complex nature of oil protection against paraquat toxicity in mice is still unknown, this study provides evidence for in vivo oxidant protection by a monounsaturated fatty acid.