Extra-hepatic Walker sarcoma 256 produced a marked decrease (approximately 60%) in the levels of cytochrome P-450 and NADP-cytochrome P-450 reductase in rat liver endoplasmic reticulum, and a lesser decrease (approximately 20%) of cytochrome b5 and NADH-cytochrome b5 reductase. Polychlorinated biphenyls induced the synthesis of these cytochromes and reductases to approximately the same extent both in normal and tumor-bearing rats. The double-label technique was used to demonstrate that the synthesis of cytochromes P-450 and b5 was reduced in the liver of tumor-bearing rats. The turnover of P-450 was not affected by the tumor, whereas cytochrome b5 turnover was decreased. It is proposed that Walker sarcoma 256 mainly affects the transcription of cytochromes P-450 and b5 through a toxohormone, and that a regulatory mechanism coordinates the level of each cytochrome and its respective reductase.