To determine injection time and effective dose of ciprofloxacin in endophthalmitis and to evaluate the effectiveness of dexamethasone. In rabbits, Pseudomonas aeruginosa (2 × 10(4) CFU/0.1 ml) was inoculated intravitreally. At 6, 12, 18, 24 hours postinoculation, single intravitreal doses of ciprofloxacin (300 microgram/0.15 ml or 100 microgram/0.05 ml) alone or with dexamethasone (400 microgram) were given. Electrophysiological and histologic measures were utilized to rate drug effectiveness. 300 micrograms ciprofloxacin was effective in killing P. aeruginosa at 6 and 12 hours postinoculation, but one hundred ug ciprofloxacin was not effective. 300 ug ciprofloxacin had no significant effect in killing P. alphaeruginosa at 18 hrs and 24 hrs postinoculation. Eyes treated with dexamethasone (400 microgram) and ciprofloxacin (300 microgram) at 6 hours postinoculation did not differ from eyes treated with ciprofloxacin alone. Cultures from eyes treated with dexamethasone and ciprofloxacin at 12 hours postinoculation were positive. Cultures from eyes treated with ciprofloxacin alone were negative. The failure of treatment at 18 hrs and 24 hrs postinoculation may be due to either an increased rate of clearance of drugs from the eyes or a reduced bactericidal effect of ciprofloxacin which could be altered by acidic pH, degree of hypoxia or bacterial counts. Dexamethasone had no beneficial effect in the treatment of P. aeruginosa endophthalmitis in the early phase.