AbstractIsoniazid (50 or 100 mg kg−l p.o.) inhibited the elimination of ethanol (0·5, 1·0, and 2·5 g kg−l p.o.) from the plasma of rabbit, guinea pig, and rat. The effect of isoniazid, isonicotinic acid, N‐acetylisoniazid, N‐acetylhydrazine, N,N‐diacetylhydrazine, and hydrazine on the in vitro metabolism of alcohol by rabbit liver alcohol dehydrogenase was examined. Only isoniazid, hydrazine, and acetylisoniazid showed significant inhibitory activity with I50's of 17·7, 1·25, and 0·78 mmol 1−1 respectively. Intolerance to ethanol following isoniazid treatment was attributed to isoniazid inhibition of liver alcohol dehydrogenase.