2,4,5-Trichlorophenoxyacetic acid and 2,6-dinitrotoluene are hazardous chemicals that have potential harmful effects. 2,6-DNT is recognized as a hepatoxicant while 2,4,5-T, a component in Agent Orange, is also suspect. 2,6-DNT requires both oxidative and reductive metabolism to elicit genotoxic effects. In order to determine what effect 2,4,5-T had on 2,6-DNT metabolism, intestinal enzymes, microbial populations, and urine mutagenicity were examined during 2,4,5-T treatment. Weanling Fischer 344 male rats were treated daily with 54.4 mg/kg 2,4,5-T by gavage for 4 weeks. 1,2, and 4 weeks after the initial dose, rats were administered (p.o.) 2,6-DNT (75 mg/kg) and urine was collected for 24 hours in metabolism cages. Azo reductase, nitroreductase, beta-glucuronidase, dechlorinase, and dehydrochlorinase activities were examined concurrently. Treatment of rats for one week reduced the transformation of 2,6-DNT to mutagenic urinary metabolites. This was accompanied by a decrease in the fecal anaerobic microorganisms. The elimination of Lactobacillus fermentum from the small intestine and cecum of treated animals accompanied a significant increase in oxygen tolerant lactobacilli and other unidentified aerobic microorganisms. (Copyright (c) 1992 by the Society of Toxicology.)