Neither the implantation of active CA nor treatment with O-ethyl,S-phenylphosphoramidothiolate (EPPAT), a potent inhibitor of the juvenile hormone esterase (JHE), prevented metamorphosis of final instar tobacco hornworms. However, a combination of the two treatments often blocked metamorphosis and caused the formation of supernumerary larvae or larval-pupal intermediates. So also, in conjunction with EPPAT treatment, unilateral severance of the medial nerve from the brain to the corpus cardiacum-corpus allatum complex often resulted in abnormal supernumerary or intermediate larval forms. Thus, clearance of JH from mature hornworm larvae prior to metamorphosis appears normally to depend on two mechanisms: (1) cessation of JH production by inhibition of the CA via the innervation of these glands, and (2) destruction of previously secreted existing JH via production of JHE. In the present experiments, each of these mechanisms appeared fully able to clear JH sufficiently to permit normal metamorphosis, because only simultaneous interruption of both mechanisms led to formation of supernumerary larvae. Acting in concert as they do late in larval life, these two mechanisms ensure the timely and thorough clearance of JH in preparation for metamorphosis.