There appear to be two major pathways for the metabolism of nitrobenzene and substituted nitrobenzenes. The first of these is reduction of the nitro group to yield aniline or substituted anilines. For nitrobenzene and perhaps for pentachloronitrobenzene, reduction of the nitro group to the amine is accomplished by bacteria of the gastrointestinal tract. Addition of a second nitro group results in easier reduction of one of the nitro groups on dinitrobenzenes, since they can be reduced under aerobic conditions by hepatic and erythrocyte enzymes. Bacterial reduction of the dinitrobenzenes is probably not quantitatively important in vivo. The second pathway is replacement of a nitro group by glutathione. The relative importance of this pathway compared to nitro group reduction depends upon the compound. It has not been demonstrated to occur for nitrobenzene. It is the major route of metabolism for 1,2-dinitrobenzene but is not an important route for 1,3- or 1,4-dinitrobenzene in hepatocytes. Tetrachloronitrobenzene isomers in which the nitro group is flanked by chlorines and pentachloronitrobenzene undergo nitro group replacement, but 2,3,4,5-tetrachloronitrobenzene does not. The most important pathway for the metabolism of mononitrotoluenes is methyl group oxidation. All quantitatively important metabolites are apparently formed from the nitrobenzyl alcohols. The mono- and dinitrotoluenes are not significantly reduced to isolatable metabolites by mammalian enzymes in vivo; intestinal microflora reduce these compounds after biliary excretion of the nitrobenzyl glucuronides. The little available evidence suggests that this is not the case for trinitrotoluenes. Urinary metabolites retain the methyl group and bear one or two amino groups. This suggests either that mammalian enzymes are capable of reducing the nitro groups of trinitrotoluenes in vivo or that intestinal microflora gain access to unmodified trinitrotoluene. The nitropolycyclic aromatic hydrocarbons are apparently metabolized by both nitro reduction and ring oxidation. There is good evidence, at least for 1-nitropyrene and 6-nitrobenzo[a]pyrene, that nitro reduction occurs in intestinal microflora. the complexities of foreign compound metabolism are well illustrated by the biotransformation of the nitroaromatic compounds. Positional isomers are preferentially metabolized by markedly different pathways. Substitution to different degrees or with different functional groups greatly affects the types of metabolites formed. Yet these compounds also offer opportunities for understanding the mechanisms of foreign compound metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)