The metabolism of (+)-cicletanine and (-)-cicletanine (10 mg kg-1) was studied in healthy male Wistar rats 24 hr after a single dose and following daily oral administration for 25 days. Urine, collected in 24-hr intervals on days 1, 5, 10, 15, 20, and 25, was analyzed by an HPLC method for parent drug and its sulfate/glucuronide conjugates. In urine, the sulfate and glucuronide conjugates of cicletanine were the only two major components quantitated; parent drug was a minor component. Within 24 hr after the first dose of (+)-cicletanine, the sulfate conjugate was the major urinary component; the ratio of sulfate to glucuronide conjugate was 3. After oral administration of (-)-cicletanine, the glucuronide and sulfate conjugates were present in similar amounts. For each enantiomer, the ratio of sulfate/glucuronide did not change upon multiple dosing, and inversion of the enantiomers did not occur. Although sulfate and glucuronide conjugates of each enantiomer are formed, the relative amounts of each conjugate depends on the enantiomer, indicating that there is stereospecificity in the disposition of cicletanine.