After oral application of the mushroom poison gyromitrin a time and dose dependent decrease of cytochrome P-450 was found in rat liver microsomes. The maximal decrease to about 50-60% of the control (after 200 mg/kg, 80% of LD50) was observed 8-12h after application, a normalization after 48 h. The inhibition of cytochrome P-450 mediated metabolism of aminopyrine and p-nitroanisole corresponds to the decrease of cytochrome P-450. The specific activity of cytochrome P-450 remains unchanged while that of cytochrome P-448 is decreased as shown by means of the metabolism of ethoxycoumarin or ethoxyresorufin. Comparable results were obtained after application of N-methyl-N-formylhydrazine (MFH) which is formed from gyromitrin rapidly by hydrolysis. An attack on the endoplasmatic membrane with a stimulation of lipid peroxidation is discussed.