1. The action of 1,1,1-trichloroethane (1,1,1-TCE) on cytochrome P-450-dependent mixed-function oxidation by rat liver microsomes was studied by determination of the rates of O2 consumption, H2O2 production, and 1,1,1-TCE metabolism, and from the spectral change in cytochrome P-450. 2. 1,1,1-TCE caused increases in the rate of O2 consumption, and H2O2 production although metabolism of 1,1,1-TCE was minimal. The stoichiometry of the rate of metabolism of 1,1,1-TCE to the increase in the rate of O2 consumption was about 0.011. The increase in O2 consumption and the production of H2O2 did not occur in microsomes treated with SK&F 525-A. 3. Spectral studies indicated that 1,1,1-TCE bound to cytochrome P-450 and showed a type I spectral change. 4. The addition of NADH with NADPH in the reaction medium enhanced the increase in O2 consumption caused by 1,1,1-TCE, whereas it did not change the rate of H2O2 production. 5. There was no increase in the formation of thiobarbituric acid substances in the reaction medium incubated with 1,1,1-TCE. 6. It was concluded that 1,1,1-TCE had an uncoupling effect on the cytochrome P-450-dependent mixed-function oxidation system.