The 24-hr excretion of urinary D-glucaric acid (UGA) has been measured in 5 seriously burned adults and compared with 6 healthy adults. In the burn patients mean UGA was 14.4 +/- 5.4 (+/- SD) mumoles/day and 28.7 +/- 6.5 mumoles/day in controls (p less than 0.002). In a 6-year-old female, UGA was also found to be very low. In a seventh burn patient, an adult male taking 20 mg of fluphenazine until his injury, his UGA was still in the normal range (29 mumoles/day) on the day of admission but descended to 21 mumoles/day at 2 days, to 16 at 4 days, and to 13 at 6 days. Treatment with fluphenazine was then reinstituted and on the tenth day UGA was 28 mumoles/day, indicating that after thermal injury UGA can respond to drugs. Although the inference has not been proved that decreased UGA corresponds to a decreased activity of drug metabolism, there is evidence of a strong correlation between increased UGA and increased drug metabolism. A decrease of UGA in disorders that generally lower metabolic activity supports a possible correlation in severe burns. If drug metabolism activity is lowered in the seriously burned patient, drug overdose may well result from the usual clinical doses.