In the past five years we have studied the penetration of locally applied sulfonamides into the eye, with a view toward developing new topical carbonic anhydrase inhibitors for the treatment of glaucoma.The drugs varied by 400 fold in their permeability to the anterior chamber and 20, 000 fold in permeability to the posterior chamber. We report now on two particular findings related to drug structure:1) Transcorneal permeability of the ionic or dissociated form of the drug is relatively high dissociated some 1/4 that of the undissociated form.2) Depending on the structure, certain compounds are sequestered in the cornea (presumably the stroma) and form a release system into the anterior aqueous.