Glucuronidation of 1-naphthol in the rat intestinal wall was studied in isolated perfused intestinal segments. 1-Naphthol glucuronide appeared on the mucosal as well as on the serosal side of the intestinal segments irrespective of the side (mucosal and/or serosal) on which naphthol was administered. Appearance of naphthol glucuronide was linear with time. A lag phase of 3.9 +/- 0.9 and 4.3 +/- 1.0 min was observed for the appearance on the mucosal and serosal side, respectively. Total glucuronide appearance rate after serosal administration of 10 to 100 microM naphthol was 3- to 4-fold higher than after mucosal administration. It is concluded that glucuronidation after mucosal administration is limited by the entry of naphthol into the metabolizing compartment.