This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped ganciclovir could prolong intraocular therapeutic levels when it is compared to the intravitreal injection of a simple solution of the drug. New Zealand white rabbits were given an intravitreal injection of the drug solution and of liposome-encapulated ganciclovir. The intravitreal clearance of ganciclovir was determined after a single injection of either the drug solution (200 mu g/0.1 mL) or the liposomally-entrapped (with 41% load; 82 mu g drug load and 118 mu g free) ganciclovir. The ganciclovir vitreal concentrations were measured at various time intervals for a period up to 43 days using an HPLC method. The results of this study clearly demonstrated that prolonged intravitreal drug levels (above the mean inhibitory dose of cytomegalovirus of 1 mu g/mL) after administration of the liposome-entrapped ganciclovir and estimated to continue beyond 30-43 days. The injection of the 200 mu g/0.1 mt of drug solution showed a mean vitreous concentration which was higher than the ID50 only for 55 h. The disappearance rate constant for the liposome-encapsulated injections was approximately 22 x slower than simple drug solution injections (controls). No evidence of retinal toxicity was found by clinical or light microscopy examination of the treated eyes.