3-Phenyl-5-(β-diethylaminoethyl)-1,2,4-oxadiazole is capable of producing irritation of the bladder of rats treated orally with 500 mg./kg. Other derivatives administered in high doses also caused bladder irritation. The oxadiazole derivatives that irritated the bladder were characterized by the presence, in position 5, of an aminoethyl chain in which the N was linked to 2 alkyl radicals (Me, Et) or was part of a morpholine or pyrrolidine group. The 5-octahydroazocinoethyl and N-methylpiperazinoethyl derivatives did not cause irritation. The benzene ring did not seem to be important for irritating activity, and substitutions, other than a OH group on the benzene ring, did not modify the irritating action. The results also disclosed the complete inactivity of both the nonbasic oxadiazole derivatives as well as benzamidoxime, benzamide, benzonitrile, and benzylamine, which chem. represent some degradation products of the phenyl-oxadiazole nucleus. Study of local tolerance of the products indicated no relation between the irritating action demonstrated by subcutaneous injection and the ability of producing vesical irritation, at least with the soluble compounds tested (a total of 37). That only the compounds having a dialkylaminoethyl chain irritate the bladder was related to the low chem. stability of these products which, contrary to the stable dialkylaminomethyl and dialkylaminopropyl homologs, have a tendency to easily break down into dialkylamines and vinyl derivatives The biol. effect on the bladder was attributed to the secondary amine. This was proved by the fact that the oxadiazole residues of the cleavage, and any of their possible metabolites, did not cause irritation of the bladder. Vesical irritation was related not only to the formation of diethylamine, but also to the rate at which this process took place.