The rectal absorption of gentamicin sulfate in rats, both in the presence and absence of sodium salicylate, was facilitated by the use of high ionic strength aqueous formulations. The relative order of effectiveness in promoting gentamicin absorption was sodium dihydrogen phosphate congruent to sodium chloride much greater than potassium chloride, indicating a preferential effect of sodium ions. The increased gentamicin bioavailability in response to sodium salicylate adjuvant activity appeared to be independent of and additive to the increased gentamicin absorption due to high ionic strength conditions. The inability of sorbitol to increase gentamicin bioavailability above control levels indicated that elevated osmotic pressure was not a major determinant of rectal gentamicin absorption.