S-(-)- Timolol maleate was oxidized, using the modified Pfitzner-Mofatt method, to the corresponding keto analog, which was then coupled with either hydroxylamine or methoxyamine in the same reaction medium. The products separated, timolone oxime (TO) or timolone methoxime (TMO), were found to be a mixture of both E and Z isomers with the Z isomer in higher concentration. Both isomers could be separated on silica column. No isomerization of any of the isomers could be detected whether in buffers or biological fluids. TMO salts were found to be stable in slightly acidic buffer. The Z isomer of TMO is more stable than the E isomer. Both TO and TMO showed pronounced reduction of the intraocular pressure (IOP) in normotensive rabbits, when instilled into the conjunctival sac. Reduction of IOP caused by either TO or TMO was higher than the reduction produced with the same dose of timolol maleate. Equal doses of any of the TMO isomers or the mixture of isomers gave almost the same percent reduction of IOP. TMO and TO did not show cardiovascular effects when administered intravenously to rabbits or rats. Both are good candidates to be used for topical management of glaucoma without producing systemic side effects.