Inhibitory effects of three new derivatives of 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide on bovine carbonic anhydrase have been investigated. The new compounds are 2-(3-chloropropionylamino)-1,3,4-thiadiazole-5-sulfonamide, 2-(2,2-dichloroacetylamino)-1,3,4-thiadiazole-5-sulfonamide, and 2-(3-phenylpropionylamino)-1,3,4-thiadiazole-5-sulfonamide. The new compounds inhibit the esterase activity of carbonic anhydrase noncompetitively and have inhibition constants and I ₅₀ values very similar to those for 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide, the latter being clinically used in the treatment of glaucoma.