The bioavailability of ursodeoxycholic acid (UDCA), a cholesterolic gallstone dissolving agent, has been analysed in seven healthy human volunteers. After absorption of a capsule containing a 500 mg dose, the time course of plasma concentrations of the drug presented a double peak profile over a 240 min period. In order to explain this result, a second group of five subjects bearing a four-way jejunal catheter fitted with an occluding balloon, received an oral dose of 250, 500 or 750 mg of the drug. Simultaneous analyses of plasma UDCA concentrations and jejunal UDCA contents were carried out. UDCA is poorly soluble in the gastro-duodeno-jejunal contents of fasted subjects since 21-50% of the ingested doses were recovered in solid form. The profile of plasma concentration paralleled the amount of soluble UDCA present in intestinal lumen. When jejunal contents were infused below the balloon a second plasma peak appeared in cases corresponding to ingestion of higher doses of UDCA. In conclusion, pharmacological doses of UDCA are not readily soluble in the stomach and intestine of a healthy fasting man. In consequence, the bioavailability of the drug varies with its progressive solubilization in the gastrointestinal tract. The present results suggest that repeated daily doses of UDCA should improve its bioavailability in treated gallstone patients.