BACKGROUND It was previously found that high dose intravitreal ganciclovir provided superior treatment of cytomegalovirus retinitis compared with intravenous treatment. This study examined the stability and solubility of the ganciclovir solution to determine the shelf life of prepared solution, and compared the cost of intravitreal with intravenous therapy. METHODS For the solubility studies high performance liquid chromatography was used to determine the ganciclovir concentration in various solutions. Measurements were taken of freshly made 20 mg/ml solution, the same solution stored at room temperature or frozen for 10, 17, and 24 days, after the solution was filtered, and after it was heated at 56 degrees C. For the cost comparison analysis the cost of 22 patients treated exclusively with intravitreal high dose ganciclovir was compared with cost estimates for the same patients treated with a standard intravenous therapy regimen over the same time. RESULTS There was little variation in the concentration of ganciclovir regardless of the storage conditions, suggesting that the 20 mg/ml solution was very stable. The heating and filtering experiments suggest that maximum solubility was achieved both in the freshly prepared and thawed frozen stored solution. The total cost of the intravitreal treatment was Aus $172,435 and the estimate of intravenous treatment was Aus $490,521. This represents a total saving of $318,086 (65%), or $14,458 per patient. The average number of weeks of treatment for each patient was 27.9 (613 weeks/22 patients), so the saving per patient per year was $29,946. CONCLUSIONS High dose intravitreal ganciclovir therapy may be administered in a very cost effective way, which along with its acceptability, safety, and clinical efficacy make it an attractive method of treatment of CMV retinitis.