A generalized synthesis of 3-amino-5-aryl-, 3-amino-5-poly-fluorophenyl-and 3-amino-5-alkyl-1,2,4-oxadiazoles has been developed starting from the 3-amino-5-methyl-1,2,4-oxadiazole as a common synthon. Aroylation or alkanoylation of this aminooxadiazole, followed by thermally-induced ring-degenerate equilibration of resulting 3-acylamino compounds, and final acid hydrolysis of the 3-acetylamino-5-aryl-(or 5-polyfluorophenyl-), or 3-acetylamino-5-alkyl-1,2,4-oxadiazoles counterpart which is formed, gave the expected 3-amino-5-substituted 1,2,4-oxadiazoles. In the case of some 3-aroylamino compounds, yields of final 3-amino-5-aryloxadiazoles are higher than that expected on the basis of the thermally-induced equilibrium composition, since acid hydrolysis plays a significant role in the shift of the equilibrium itself. Satisfactory direct procedures have also been described. As expected, restrictions to the above methodology were found in the synthesis of 5-perfluoroalkyl derivatives.