It is shown in rats that cross-innervation of the fast-twitch muscle extensor digitorum longus (EDL) by the nerve of the slow-twitch muscle soleus (SOL) can cause a complete transformation of the Z-band width from the fast to the slow muscle fibre type within two weeks and that it can still induce such a transformation, though usually less completely, even when impulse activity is excluded by chronical tetrodotoxin (TTX) block of the nerve. This provides a piece of clear-cut evidence for the presence of some activity-independent trophic factor in the neural determination of skeletal muscle fibre type.