1. The transport of 5-fluorouracil, uracil and thymine has been studied with isolated jejunal loops of rat small intestine. High performance liquid chromatography was used to identify the pyrimidines and measure their concentrations.
2. When the lumen of the intestine was perfused with 5-fluorouracil or uracil at 0.1 mmol/l or 0.2 mmol/l, the concentration in the serosal secretions was significantly higher than that in the lumen. For thymine the serosal concentration exceeded that in the lumen only at 0.1 mmol/l.
3. Analysis of the mucosal tissue water at the end of the perfusion demonstrated that when the intestinal lumen was perfused with any one of the three pyrimidines at 0.1 mmol/l or 0.2 mmol/l the concentration within the tissue was significantly above that in the lumen.
4. After an initial lag period linear rates of transport from the lumen to the serosal secretions were obtained for all three pyrimidines over a 10-fold concentration range from 0.1 mmol/l to 1 mmol/l.
5. Uracil and thymine inhibited the transmural transport of 5-fluorouracil.
6. The transport of 5-fluorouracil was also studied with a vascularly perfused preparation of rat small intestine. At 0.1 mmol/l the rate of transmural transport of the drug in this preparation was substantially higher than in the jejunal loops. This difference was eliminated by adding 5-fluorouracil to the vascular perfusate, suggesting that the higher transport rate in the vascularly perfused preparation was due to the lower serosal drug concentrations in the mesenteric circulation of the perfused intestine.
7. At a concentration of 5 mmol/l 5-fluorouracil inhibited water transport in the isolated loops and transmural D-galactose transport in the vascular perfusions.