2-Methylisoborneol (MIB) is a natural product produced by an assortment of microorganisms that inhabit ponds used for the raising of various fish species, including the channel catfish (Ictalurus punctatus). This and other compounds are the causative agents responsible for “off-flavor” in fish aquaculture. The similarity in structure to the cytochrome P450 mono-oxygenase substrate, camphor indicated that this enzyme system may be responsible for the metabolism of MIB in catfish. Juvenile catfish (200 g) were exposed to 10 ppm of MIB for 24 h. Another group of catfish received an intraperitoneal injection of 1 mg/kg MIB 24 h prior to cytochrome P450 examination. Cytochrome P450 content was measured spectrally and by Western-blot analyses using anti-trout P450 polyclonal antibodies in the liver of each animal and the pooled kidneys of each group and compared to the appropriate controls. Total cytochrome P450 content as measured spectrally was not affected by treatment with MIB in either liver or kidney. However, specific isoenzymes were differentially expressed in each tissue. For example, in kidneys of animals injected with MIB, CYP IA was induced almost 2-fold, while CYP IA was unchanged in animals given water-borne MIB. In the livers of animals from water-borne MIB exposures, an 81% increase in a CYP 2K1 orthologous form was observed. Repression of various constitutive P450s were also seen. Significant differences in isoform expression were observed between injected fish and those receiving water-borne exposures of MIB. These results suggest that MIB caused the upregulation and downregulation of various cytochrome P450 isoforms in the liver and kidney of channel catfish. Moreover, kidney P450 (CYP IA) and/or a liver CYP 2K1 orthologue may play a role in the biotransformation of MIB to water-soluble metabolites and subsequently enhance its elimination.