Agglomerated crystals of enoxacin were prepared by a novel spherical crystallization technique using ammonia diffusion system (ADS). This technique made it possible to agglomerate amphoteric drugs like enoxacin which could not be agglomerated by the conventional means. When an ammonia water solution of enoxacin was poured into the mixture of acetone and a water-immiscible solvent such as dichloromethane under agitation, a small amount of ammonia water was liberated in the system. The ammonia water played a role both as a good solvent for enoxacin and a bridging liquid, which collected fine crystals precipitated into spherical agglomerates in one step. Moreover, agglomerates of the stable crystalline form were obtained by selecting the proper solvents. It was proved that the agglomeration mechanism follows these steps : acetone in the crystallization solvents enters into droplets of ammonia water and consequently enoxacin dissolved in the ammonia water is precipitated, while the droplets collect the crystals; simultaneously, a part of the ammonia in the agglomerates diffuses to the outer organic solvent phase.