For several hours after a single intraperitoneal (i.p.) dose to mice, piperonyl butoxide, 2-methylpropyl 2-propynyl phenylphosphonate (NIA 16824), and 5,6-dichloro-l, 2,3-benzothiadiazole (WL 19255) inhibit hepatic microsomal mixed-function oxidase (mfo) activity and the apparent level of cytochrome P-450 but, after 24–72 hr, they induce increased mfo activity and P-450 content. Other types of insecticide chemical synergists studied are generally less active or inactive in this respect. The active compounds enhance the toxicity of several insecticide chemicals and markedly prolong hexobarbital sleeping time but not hexobarbital toxicity. The action of WL 19255 differs from that of piperonyl butoxide and NIA 16824 in that it is relatively non-specific in inhibiting enzymatic activity on several substrates, gives a more prolonged effect on P-450, and the magnitude of induction is greater.