The effects of xenobiotics on in-vitro hepatic enzymes activity and in-vivo urinary D-glucuronic-acid excretion were investigated in rats and guinea-pigs. Male Wistar-rats and male guinea-pigs were administered the following compounds intraperitoneally (doses in milligrams per kilogram per day (mg/kg/day)): hexachlorobenzene (118741), heptachlor (76448), disulfiram (97778), perthane (72560), toluene (108883), tetraethyl-lead (78002). Aroclor-1260 (11096825), ethanol (64175), n-hexane (110543), Dodin (2439103), atrazine (1912249), dimethoate (60515), nitrobenzene (98953), aniline (62533), benzene (71432), or phenylmercuric-acetate (62384). For in-vitro studies, liver homogenates were examined for N-demethylation of aminopyrine and UDP-glucuronyltransferase activity on p-nitrophenol. The urinary excretion of D-glucuronic-acid was measured in-vivo in guinea-pigs following xenobiotic treatment. Rats were also treated for 8 hours with 150mg/kg sodium-barbital (144025), 130mg/kg phenobarbital (50066) or nikethamide (59267), all intraperitoneally, or 150mg/kg chlorbutol (57158) or 60mg/kg DDT (50293) by mouth. Effects on enzyme activity and D-glucuronic-acid excretion were examined. Results were compared with saline or sesame-oil treated controls. Only disulfiram, ethanol, and aniline treatment enhanced the rate of N-demethylation and glucuronidation. Perthane, tetraethyllead, Dodin, and dimethoate increased N-demethylation while hexachlorobenzene, Aroclor-1260, n-hexane, nitrobenzene, and benzene enhanced glucuronidation. Only phenylmercuric-acetate inhibited urinary D-glucuronic-acid excretion. Only dimethoate, nitrobenzene, aniline, and benzene did not increase excretion of D-glucuronic-acid. No alteration in enzyme activities were found in short term drug administration in rats although all compounds caused significant enhancement of D-glucuronic-acid excretion. The authors conclude that stimulation of the D-glucuronate pathway, resulting in enhanced D-glucuronic-acid excretion, is not necessarily related to an induction of the drug metabolizing enzymes.