• The ability of collagen-shield therapeutic contact lenses to release gentamicin sulfate and vancomycin hydrochloride individually and in combination was investigated using a fluorescent polarization immunoassay. In vitro studies showed that presoaked collagen shields released the majority of gentamicin within the first 30 minutes of elution, while vancomycin was released gradually over six hours of elution. Three experiments in rabbits compared the gentamicin and vancomycin levels produced at five time points in tears, cornea, and aqueous humor by collagen shields soaked in antibiotics vs frequent-drop therapy. The collagen shields soaked in gentamicin, vancomycin, or a combination of the two produced tear, cornea, and aqueous humor levels that were generally higher or at least comparable with those achieved by frequent-drop therapy.