Botulin type A was injected into the eyelids of adult monkeys, and structural alterations in the orbicularis oculi muscle were evaluated after survival times of 7 to 84 days. The most profound change seen at both the light- and electron-microscopic levels was nonselective atrophy of virtually all muscle fibers. Moreover, the botulin-induced blockade of neuromuscular transmission was nonspecific in producing alterations in the three orbicularis fiber types. Muscle structural changes appeared to be reversible, with no apparent long-term consequences. While sprouting of preterminal axons was noted in botulin-treated muscle, formation of collateral sprouts did not appear to be widespread. These changes contrast with the fiber type-specific, long-term alterations induced in extraocular muscle by botulin treatment. However, this differential response may be attributed to the very clear differences in fiber type composition and motor control mechanisms between eyelid and extraocular muscle groups. The efficacy of botulin treatments for strabismus and focal dystonia may then be directly related to both the anatomic fiber type composition and the functional properties of motor control systems of the injected muscle.