The effect of the mode of administration on the intraocular penetration of gentamicin in rabbits with bacterial endophthalmitis was examined. Animals were treated over a period of 12 hr either by intramuscular injection every 3 hr or by continuous intravenous infusion; both groups received the same total dose of drug. The mean peak and trough levels in serum with intramuscular injection were 11.4 and 1.6 micrograms/ml, respectively. Mean serum levels during continuous infusion were approximately 7 micrograms/ml. The area under the time-concentration curve for serum was approximately the same in both groups. Mean vitreous humor levels at the end of therapy were 2.8 micrograms/ml in the animals treated by repeated intramuscular injection and 2.6 micrograms/ml in those treated by continuous infusion (P greater than 0.2). In this model, the intraocular penetration of gentamicin was not influenced by the mode of systemic administration.