Transscleral iontophoresis has been suggested to be a potentially useful noninvasive technique in intravitreal introduction of ionizable drugs, such as cefazolin sodium, ticarcillin disodium, and gentamicin sulfate. To investigate the usefulness of this technique in the administration of corticosteroids, we performed transscleral iontophoresis of dexamethasone sodium phosphate (300 mg/mL, 20 mmol/L edetic acid [EDTA]) into rabbits at a current of 1.6 mA for 25 minutes. Eyes were enucleated at different time intervals and frozen in liquid nitrogen. The frozen vitreous bodies and adherent sensory retina were collected and sonicated, and dexamethasone levels were measured using high-pressure liquid chromatography. In addition, to study the facilitation of drug transport by cryotherapy, a second group of rabbits were given a single application of cryotherapy (-78 degrees C, 45 seconds) 3, 7, and 14 days before iontophoresis in the same region. Without cryotherapy, the initial level of dexamethasone in the vitreous body-sensory retina after iontophoresis was 139.3 +/- 51.5 mg/L (mean +/- SE) (n = 6) with a half-life of less than 2 hours. In the cryotreated group, the levels of dexamethasone immediately after iontophoresis 3, 7, and 14 days after cryotherapy were 61.5 +/- 31.7 (n = 6), 88.4 +/- 55.1 (n = 6), and 112.2 +/- 32.5 (n = 6) mg/L, respectively, indicating that levels were lower compared with the group without cryotherapy. Our results suggest that a high dose of dexamethasone can be delivered by using this noninvasive technique and that cryotherapy before iontophoresis does not increase drug levels in the vitreous body.