The interactions of sucralfate with colistin sulfate, with tobramycin sulfate, and with amphotericin B were studied. Sucralfate 500 mg was added to 40 mL of distilled water adjusted to pH 3.5 with hydrochloric acid. Stock solution of one of the three antibiotics was added to give a final colistin concentration of 50 mg/L (as the sulfate salt), final tobramycin concentration of 50 mg/L (as the sulfate salt), and final amphotericin B concentration of 25 mg/L. Samples were removed from each sucralfate-antibiotic mixture at 0, 5, 10, 15, 30, 45, 60, and 90 minutes and analyzed for antibiotic concentration by high-performance liquid chromatography (colistin), enzyme immunoassay (tobramycin), and spectrophotometry (amphotericin B). To determine if any interaction was reversible, the mixtures were stored for 90 minutes without sampling, the pH was adjusted to 6.5-7.0, and samples were removed and analyzed. All tests were performed in triplicate, and the temperature was maintained at 25 degrees C. Significant drug loss was observed starting at five minutes for each antibiotic-sucralfate mixture. This effect was not reversible in the less acidic environment. The concentrations of colistin, tobramycin, and amphotericin B declined rapidly when each drug was combined separately with sucralfate.