Penetration of ceftazidime, a third generation cephalosporin, into the vitreous cavity after intravenous administration was investigated. Because antimicrobial penetration varies with surgical status of the eye and with inflammation, studies were conducted in phakic, aphakic, and aphakic, vitrectomized eyes in both normal and inflamed conditions. Ceftazidime 50 mg/kg was administered every 8 hours and vitreous cavity concentrations were tested at intervals from 2 to 72 hours after the initial dose. No penetration was found into control phakic and aphakic eyes, but drug concentrations were detected in inflamed eyes at 24 hours. Vitreous concentrations of ceftazidime in aphakic, vitrectomized eyes reached levels well above the minimal inhibitory concentration (MIC) for Pseudomonas organisms within 2 hours of intravenous administration in control eyes (8.5 micrograms/ml) and inflamed eyes (35.4 micrograms/ml). Inflammation and removal of the lens and vitreous significantly enhanced ceftazidime penetration at all time periods tested. Ceftazidime penetrates into the vitreous cavity of inflamed eyes after intravenous administration and achieves concentrations above the MIC for Pseudomonas organisms. Penetration is greatest in aphakic, vitrectomized eyes.