Induction of cytochrome P-4501A protein and induction of related enzyme activity are hallmark physiological responses following exposure to planar halogenated aromatic hydro carbons (HAHs) such as 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126; PeCB). Environments contaminated by HAHs are often contaminated by mixtures of anthropogenic contami nants, including organometallic compounds. Both HAHs and organometallics easily bio-concentrate and bioaccumulate in aquatic food chains that may ultimately be linked to humans through seafood consumption. Tributyltin (TBI), a marine biocide, has been detected in many aquatic environments due to its primary use as a marine antifoulant agent. Exposure to TBI, as well as several PCBs, has been associated with immunotoxicity, neurotoxicity, and endocrine disruption. Recently TBT has been shown to inhibit cyto chrome P-4501A activity in vitro, but information concerning these effects in vivo and in combination with classical inducers of P-4501A, such PeCB, is lacking. We exposed female B6C3F1 mice to 0.01, 0.1, and 1.0 mg/kg PeCB, TBI, or both in combination, with corn oil (CO) serving as a carrier control. Cytochrome P-4501A protein levels and related benzolalpyrene hydroxylation (BaP-OHase) activity were measured following a sin gle acute intraperitoneal dp) dose or seven daily injections. Body, thymus, and liver weights were used to monitor general physiological responses following exposure. P-4501A levels and BaP-OHase activity were significantly elevated in mice exposed to PeCB alone. This effect was enhanced by coexposure to low levels of TBT; PeCB-induced P-4501A-related activity was potentiated at the low range of each. The highest dose of TBT, however, inhibited these activities when given in combination with PeCB. Thymic atrophy was evident only in mice exposed daily to 0.1 and 1.0 mg/kg PeCB alone, or to a combi nation of the lowest and highest dose of PeCB and TBT, respectively. Because environ mental levels of TBT are not expected to be as high as the highest level used in our toxi-cological studies, we conclude that environmental exposure to TBT may potentiate, rather than inhibit, the activity of environmental levels of HAHs that are associated with P-4501A induction.