A series of bicyclic 1,3,4-thiadiazolo[3,2-a]pyrimidine- and 1,3,4-thiadiazolo[3,2-a]triazine-7-sulfonamides were synthesized from 5-amino-1,3,4-thiadiazole-2-sulfonamide and evaluated for topical efficacy as ocular hypotensive agents. The compounds were tested for the physicochemical properties of sulfonamide pKa, free acid water solubility, CHCl3/buffer partition, and transcorneal penetration (kin), as well as for activity against carbonic anhydrase (I50). A number of these compounds exhibited lower sulfonamide pKa and higher water solubility than those of acetazolamide (1) and methazolamide (2), and one, 12, brought about a small reduction in IOP in the normal rabbit eye.