According to clinical reports, several therapeutic agents produce ethanol intolerance, which is often referred as disulfiram reaction. The mechanism of this manifestation was investigated in the Wistar rat, by measuring the alcohol and aldehyde dehydrogenases (ADH, ALDH) of the liver and the brain after subacute administration of chloramphenicol (100 mg/kg X 4, intraperitoneally), chlorpropamide (80 mg/kg X 4, intraperitoneally), disulfiram (150 mg/kg X 4, intraperitoneally), griseofulvin (100 mg/kg X 4, intraperitoneally), isoniazid (200 mg/kg X 4, intraperitoneally), metronidazole (200 mg/kg X 4, intraperitoneally), and procarbazine (100 mg/kg X 4, intraperitoneally). All substances tested decrease the activity of the low-Km ALDH in the brain, with the exception of griseofulvin. The hepatic low-Km enzyme is also inhibited, with the exception of griseofulvin and metronidazole. The high-Km ALDH responds in an inconsistent way, while ADH is not affected at all. The results suggest that the so-called "disulfiram-reaction" is mediated mainly, but not exclusively, by inhibition of the low-Km ALDH.