Ciprofloxacin has been proposed for the systemic treatment of endophthalmitis. We studied the role of therapy based on the susceptibility of actual bacterial isolates and developed a system for assessing this susceptibility in endophthalmitis. Susceptibility testing was performed on 68 bacterial isolates from 66 patients with endophthalmitis. Our results indicated that, on the basis of a vitreous ciprofloxacin concentration of 0.25 microgram/ml, only 41 of 68 isolates (60%) would be inhibited by systemic therapy. All gram-negative bacteria (six of six) would be inhibited, whereas gram-positive bacterial susceptibility was variable. We concluded that systemic ciprofloxacin alone should not be administered empirically but it could provide an adjunct for treating selective cases of bacterial endophthalmitis. Bacterial susceptibility should be assessed on a blood serum standard of 0.25 microgram/ml instead of 1.0 microgram/ml.