2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a contaminant of some herbicides, is an extremely potent enzyme inducer. Male albino rats of two genetically different substrains developed for the inducibility (RR) and noninducibility (rr) of aldehyde dehydrogenase by phenobarbital were given TCDD 80 microgram/kg as a single dose 6 days before analysis. rr-Animals having no induction of the hepatic soluble high-Km aldehyde dehydrogenase by phenobarbital showed an approximate 25-fold increase in activity after TCDD treatment. The increase in aldehyde dehydrogenase activity could be detected only when measured with a millimolar substrate concentration. The aldehyde dehydrogenase activity in serum was increased 3-fold after TCDD administration in both substrains.