To investigate the enzymatic basis of the chlorpropamide-alcohol flush reaction (CPAF) we compared the isoenzyme profiles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) from liver biopsies, and of ALDH alone from erythrocytes and leucocytes, in CPAF-positive and CPAF-negative subjects. No differences were seen in ADH or ALDH phenotypes, or in the relative activities of the isoenzymes, between the two groups before chlorpropamide was given; in particular, no subjects showed the 'null' ALDH phenotype that is associated with the alcohol flush reaction in oriental subjects. There was a significant decrease in erythrocyte ALDH activity after 7 days' treatment with chlorpropamide in CPAF-positive individuals but no such difference was seen in CPAF-negative subjects. These results indicate that CPAF has a different enzymatic basis from the alcohol flush reaction of oriental subjects and suggest that in CPAF-positive subjects erythrocyte ALDH may be particularly susceptible to inhibition by chlorpropamide.