The influence of melanocortins on the process of collateral sprouting has been investigated in rat soleus muscle. The soleus muscle was partially denervated by transecting and ligating the L5 mixed nerve. Collateral sprouting was assessed by means of isometric twitch tension measurements of soleus motor units that remained following L5 transection. The smaller the number of remaining soleus motor units, the larger the extent of collateral sprouting. Seven days following partial denervation, the index of sprouting (ratio between twitch tension of motor units in partly denervated muscles and in normal muscles) was significantly increased by treatment with the ACTH4-9 analog Org.2766 (1 microgram/48 hours). This increase appeared to be present also 28 days following partial denervation. The electrophysiological results were confirmed by histological investigations. The results provide evidence that Org.2766 increases the motor neuron collateral sprouting capacity of peripheral nerve. Org.2766 did not induce muscle fiber hypertrophy.