The intestinal mucosal metabolism of ethinyloestradiol (EE2) and paracetamol (P) has been studied in vitro in Ussing chambers. Histologically normal jejunum or ileum was obtained from 19 patients undergoing various resections. The muscularis externa was stripped off the mucosa and the mucosal sheets mounted between two perspex chambers. Tissue viability was routinely assessed by measurement of the transmural potential difference. The percentage of steroid in the serosal chamber, 2 h after addition of EE2 (2 microCi; 80 ng) to the mucosal chamber was 2.3 +/- 0.8% (mean +/- s.d.) which comprised unconjugated drug (0.4 +/- 0.3%), sulphate conjugates (0.7 +/- 0.5%) and glucuronides (0.9 +/- 0.8%). In the mucosal chamber, 56.6 +/- 11.4% was unconjugated steroid, 33.3 +/- 12.4% sulphate conjugates and 2.1 +/- 2.3% glucuronides. Small amounts of the oxidation products 2-hydroxy and 16-hydroxy-EE2 were present. At 2 h, the percentage of paracetamol in the serosal chamber was 3.2 +/- 1.4% (of added P; 2 microCi; 50 ng) of which 0.5 +/- 0.3% was paracetamol sulphate (PS) and 0.1% was paracetamol glucuronide (PG). In the mucosal chamber 2.4 +/- 0.8% and 1.0 +/- 0.2% was present as PS and PG respectively. The total amount of paracetamol conjugated was approximately 4.0%. When paracetamol in the mucosal chamber was increased to 50 micrograms (i.e. by a factor of 1000) there was a decrease in the percentage of added drug metabolized to PS and an increase in formation of PG. The glucuronide:sulphate ratio was increased from 0.34 to 3.56. Competition for sulphation was evident when both paracetamol and EE2 were presented to the intestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)