The ability of a series of naturally occurring pyrethrin synergists to inhibit various pathways of drug metabolism has been studied in the rat and mouse. These compounds were effective in vitro inhibitors of the oxidative metabolism of aniline, aminopyrine, diphenyl and hexobarbital by liver preparations. Reduction of the azo dye neoprontosil was not inhibited. In vivo inhibition of hexobarbital oxidation in the mouse, as shown by an increase in sleeping times, was also observed. Some considerations of structure-activity relationships are discussed. Several of the compounds studied produced dilation of the endoplasmic reticulum and the Golgi apparatus of liver cells as well as depleting glycogen deposits. These effects did not appear to be related to inhibitory power. These substances can alter membrane permeability, as shown by measurements of glucose exit from red blood cells. The effect on the liver and red blood cell may be a function of lipid solubility or, more likely, ability to bind to protein.