The in vivo effects of the intraperitoneal administration of an Urtica urens L. (dwarf nettle) seed extract were examined on the hepatic, pulmonary, and renal cytochrome P450-dependent monooxygenase activities of rats co-administered with 3-methylcholanthrene (MC). Urtica extract was administered by intraperitoneal injection to male Wistar rats at 200 mgkg(-1)day(-1) for 4 days from which were also co-administered with intraperitoneal injection of 50mg of MC kg(-1) of body weight twice on days 1 and 3. MC treatment increased the 7-ethoxyresorufin O-deethylase (EROD) activity of the liver, lung, and kidney 54-, 21-, and 119-fold, respectively. Urtica treatment substantially reduced the 3MC induction of hepatic, lung, and renal EROD activity by 79, 42, and 50%, respectively. Similarly, compared with the control, MROD activities in liver and kidney were increased after MC administration, and these increases were significantly inhibited by Urtica. reverse transcriptase-polymerase chain reaction (RT-PCR) analysis clearly showed that the hepatic CYP1A1 and CYP1A2 mRNA levels substantially increased after treatment with MC, which was suppressed by Urtica supplementation. Western blotting studies also supported the alterations observed in the catalytic activities and mRNA levels. In conclusion, substantial reduction in CYP1A1 and CYP1A2 expression levels and related activities with Urtica are possibly associated with a potential chemoprotective ability of the Urtica due to the anticipated decrease in the activation of environmental chemical carcinogens through modulation of the CYP1A enzymes.