During reinnervation of the completely denervated rat hind limb we observed previously a temporary overproduction of acetylcholinesterases in the soleus but not in the extensor digitorum longus muscle. In the present study, we investigated whether the predominantly slow soleus, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the extensor digitorum longus. Local denervation of the rat soleus was carried out to eliminate reinnervation by axons destined for other muscles. This produced an overshoot in AChE activity that was qualitatively similar to that observed with high sciatic crush. Local denervation of the soleus in the guinea pig was done because this muscle is composed solely of slow (type I) fibers, thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the soleus. We concluded that the neural control of AChE is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle. How these neural influences are translated into muscle synthesis and degradation remains unknown.