• A study was undertaken to determine whether the antiesterase activity of echothiophate iodide would prevent the conversion of dipivefrin to epinephrine. Dipivefrin was administered singly and in combination with echothiophate to 24 adult rabbits. Administration of dipivefrin lowered the intraocular pressure (IOP) 8 ± 1 mm Hg (P <.001). When echothiophate was given before and concomitant with dipivefrin, there was no further decrease in IOP compared with that produced by echothiophate alone (5 ± 1 mm Hg). Addition of epinephrine to eyes receiving dipivefrin plus echothiophate resulted in a significant additional decrease in IOP of 4 ± 1 mm Hg (P <.001). When echothiophate was given after dipivefrin had lowered the IOP and both drugs were continued, the IOP rose to baseline levels. These results fit the theory that the esterase converting dipivefrin to epinephrine is inactivated by cholinesterase inhibitors. The clinical use of cholinesterase inhibitors and dipivefrin may be contraindicated.