This observation motivated the hypotheses that these herbivores may also respond differently to nicotine ingestion and that these differences would influence the larvae’s interactions with their natural enemies. To determine whether M. sexta can further oxidize ingested nicotine oxides, we fed each nicotine oxide separately to M. sexta larvae in an artificial diet. We selected feeding because it is the easiest and the most natural administration method and by feeding one can readily assess the effect of these compounds on larval mass and mortality, from which we could infer if a given oxide was indeed less toxic than nicotine. Mass of M. sexta larvae fed artificial diet containing nicotine oxides was not greater than those fed nicotine-diets and larvae fed artificial diet containing NNO and cotinine gained significantly less mass than did nicotine-fed larvae. Interestingly, during the 10 d feeding, 18% of the cotinine feeding larvae died and,10% melanized, suggesting that cotinine is more toxic to M. sexta than nicotine. No further oxidized products of the nicotine oxides were found in the larval hemolymph and frass, which contained only the metabolite that the larvae ingested. We used Waldbauer assays to quantify the flux of ingested nicotine oxides through the larvae, to determine whether nicotine or its oxidation products are metabolized or excreted with different efficiencies. Excretion of the nicotine oxides during the Waldbauer assay was similar to that of nicotine for all compounds tested and these compounds were stable in the frass during the 24 h of assay. However, the Waldbauer assay can only evaluate the efficiency of excretion over a 24 h feeding trial, and hence is limited in its abilities to detect differences in the rate of excretion. Hence, to compare the clearance rates of nicotine and nicotine oxides from larval hemolymph, we injected these compounds directly to the hemolymph and periodically measured their concentration in hemolymph until 6 h, when all the metabolites attained their steady clearance rate. Recently, in a race of the polyphagous aphid, Myzus persicae that thrives on cultivated tobacco, Bass et al. conclusively demonstrated that nicotine is oxidatively detoxified. Such conclusive evidence of oxidative detoxification M. sexta has been lacking despite more than 50 years of research. We conducted an unbiased examination of M. sexta’s nicotine metabolism and obtained results consistent with the rapid excretion theory but not with the oxidative detoxification theory. Oxidative nicotine metabolites were not found in larvae from M. sexta laboratory colonies, collections from nature, and the closely related species, M. quinquemaculata. Differences from the results presented here and previous studies reporting nicotine oxidation in M. sexta could be ascribed to differences in experimental design and methods.