Bisacodyl (BIS), the parent diphenol (DES) and its sulphuric acid di-ester (picosulphate = PICO) were given by stomach tube to fasted rats at a dose of 3.1 mumol/100 g rat. Bile was sampled in the periods 0-6, 6-12 and 12-18 hrs after drug administration, and assayed for total diphenol (= free + conjugated) by HPLC. Mean fractions (% of dose +/- S.E.M.) excreted in 5 rats per compound and period were: BIS 74.0 +/- 4.7, 51.9 +/- 7.9 and 30.8 +/- 2.5; DES 41.2 +/-4.3, 46.8 +/- 4.7 and 25.1 +/- 2.5; PICO 9.0 +/- 0.9, 26.0 +/- 5.4 and 19.6 +/- 3.1. Only minor amounts were excreted as free diphenol. Urine samples taken by bladder puncture and assayed as above furthermore showed that the renal excretion of total diphenol was insignificant compared to the amounts excreted in bile. Practically no diphenol was present in urine 0-6 hrs after the administration of PICO. In experiments with BIS and DES at 0.85 mumol/100 g, total diphenol excreted in bile during 0-6 hrs was: BIS 67.1 +/- 2.6 (n = 5); DES: 55.4 +/- 3.0 (5). - The latency time for laxative effect was studied in groups of 10 unfasted rats per compound. cumulative time response curves showed that PICO caused diarrhoea more promptly at 0.85 mumol/100 g than either BIS or DES. In most rats, this delayed action of BIS and DES persisted also at 1.7 mumol/100 g. At 3.1 mumol/100 g, however, the majority of the rats reacted as promptly to these two compounds as to PICO. These results are discussed in relation to the biliary excretion experiments, and interpreted in terms of the relative importance at the different dose levels of: 1. The enterohepatic recirculated fraction, and 2. The non-absorbed fraction, which passes directly to the large intestine. For PICO, the latter fraction is the single determinant of the effect, which is triggered when the di-ester is being hydrolyzed to active diphenol in this part of the GI-tract.