The clearance of intravitreally injected triamcinolone acetonide was monitored by both indirect ophthalmoscopy and high-performance liquid chromatography (HPLC) and found to be more rapid than previously reported by others. Twenty-four rabbits were intravitreally injected in each eye with 0.4 mg of triamcinolone acetonide. Three rabbits each were sacrificed at intervals ranging from one hour to 46 days. The vitreous was then harvested and processed for HPLC analysis. Triamcinolone and the internal standard prednisolone were identified and quantitated by the use of HPLC, which was found to be both sensitive and specific for the steroids. The half-life as determined by HPLC was 1.6 days, the level at 13 days postinjection was 66 +/- 19 micrograms, and no drug was detectable by HPLC analysis at 21 days in five of six eyes. The intravitreal masses thought to be triamcinolone were clinically observable to an average of 23.3 days. The chromatographically determined clearance rate did not correlate well with clinical impressions based on indirect ophthalmoscopy.