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Dexamethasone-21-tertiary butyl acetate (dexamethasone TBA) and dexamethasone alcohol at concentrations of 0.2, 0.1, 0.01, and 0.001% were topically instilled into the right eyes of groups of 10 rabbits for 21 consecutive days. Vehicle control and untreated control groups were used for comparative evaluation. The dose-dependent changes for each compound were (1) lipid and glyocogen infiltration of liver, (2) hydropic changes of liver, (3) vacuolation and multifocal hepatic necrosis of liver, (4) atrophy of Peyer's patches of intestines, (5) white pulp atrophy of the spleen and (6) atrophy of the adrenal cortex. No pathological changes were noted for other tissues including the eye. In conclusion, the results indicate that systemic histopathologic changes for both steroids were comparable and typical for steroids.