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The mutagenicity of 4-monochlorobiphenyl (PCB3) in the liver of male 344 Fisher transgenic rats has been established by Lehmann et al (2007). The evidence that PCBs can be deposited in the lung and bound to a protein creates a need to assess the effect of mutagenic effect of PCBs in the lung. The goal of this study was to assess the mutagenicity of PCB3 in the lung of male 344 Fisher transgenic rats. Big Blue® 334 Fisher transgenic rats were given weekly intraperitoneal injections with corn oil as a negative control, 3-methylcholanthrene (3-MC) as a positive control, PCB 3 or 4-hydrox-PCB 3 (4-OH- PCB 3) weekly for 4 weeks. Lungs were removed and analysis performed to determine mutant frequency, mutation spectra, and pathological changes. There was a 2-fold increase in mutant frequency after treatment with PCB 3 and 4- OH-PCB 3 that was not statistically significant. There were changes in the mutation spectra after treatment with PCB 3 or 4- OH-PCB 3. This study shows that PCB 3 and 4-OH-PCB 3 may create mutations in the lung following exposure.