Oral administration of 3 g of ascorbic acid 1.5 hr after an oral dose of 1 g of acetaminophen caused a rapid and pronounced decrease in the excretion rate of acetaminophen sulfate in five healthy adult volunteers. There was a statistically significant increase in the fractions of the dose of acetaminophen excreted as such as as acetaminophen glucuronide but a decrease in the fraction excreted as acetaminophen sulfate. The apparent biological half-life of acetaminophen increased from 2.3 +/- 0.2 (mean +/- SD) to 3.1 +/- 0.5 hr. Concomitant administration of sodium sulfate prevented these effects. Ascorbic acid, which itself is metabolized in part to the sulfate, inhibits the conjugation of acetaminophen with sulfate by competing for available sulfate in the body.