The transepithelial intestinal elimination of ciprofloxacin was studied in a rat model. Two jejunal and one ileal segment, along with their intact blood supplies, were isolated and continuously perfused. Following a single parenteral administration of 25 mg/kg ciprofloxacin, the drug in amounts of 1.97 +/- 0.70, 1.88 +/- 0.99, and 1.44 +/- 0.77 micrograms/cm2 of mucosal surface was recovered over 90 min from the proximal and distal jejunal loops and the ileal loop, respectively, reaching a calculated fraction of 6%-7% of the dose eliminated in the entire small intestine. The rate of intestinal elimination related linearly to the parenteral dose. In the proximal jejunum, however, doses > 25 mg/kg were not accompanied by a concomitant increase in the eliminated fraction, suggesting a saturable transport process. Parenterally administered probenecid, amoxicillin, and nifedipine and changes ranging from 6.0 to 8.5 in the pH of the perfusates did not alter transepithelial elimination. This pathway of elimination of ciprofloxacin may play an important role in curing intestinal infections.