Ascorbic acid or thiamine was administered, i.p., to male mice 1 1/2 hours prior to i.p. administration of acetaldehyde. Ascorbic acid reduced acetaldehyde mortality at doses between 16 mmole/kg to 18 mmole/kg. Thiamine reduced acetaldehyde-induced mortality at lower acetaldehyde doses (16 mmole/kg) but not at higher doses (17 and 18 mmole/kg) that induced 100% mortality. Simultaneous coadministration of acetaldehyde and ascorbic acid caused a reduction in mortality. The effect of ascorbic acid or thiamine pretreatment on disulfiram-ethanol-induced mortality was investigated. A single dose of thiamine (0.24 mmole/kg) given 1 1/2 hours prior to administration of ethanol (11 mmole/kg to 88 mmole/kg) in disulfiram-treated mice reduced disulfiram-ethanol-induced mortality but a single dose of ascorbic acid (2 mmole/kg) pretreatment had no effect. Increasing the ascorbic acid pretreatment dosage schedule to three days resulted in a reduction of disulfiram-ethanol mortality. These results indicate that thiamine HCl was more potent than ascorbic acid in reducing the mortality induced by acetaldehyde or disulfiram-ethanol. The effect of disulfiram on ascorbic acid or thiamine activity toward reduction of acetaldehyde-induced mortality was investigated. The same three-day pretreatment condition for disulfiram and ascorbic acid or thiamine was used in mice as in the above disulfiram-ethanol study. In the third day, acetaldehyde was given to the mice. Either vitamin was ineffective in reducing the mortality induced by disulfiram-acetaldehyde.