To investigate the role of innervation and to determine if the process of muscle differentiation is preprogrammed, the expression of insulin-like growth factors (IGF-I and IGF-II), troponin I and troponin T mRNAs was studied in regenerating transplants of rat Extensor digitorum longus muscle in the presence and absence of nerve. The role of innervation was further investigated by denervating some adult fast (Gastrocnemius and Plantaris) and slow (Soleus) skeletal muscles. In normal adult skeletal muscles, IGF-I, IGF-II and developmental fast troponin T mRNA containing exon y, are undetectable or present at very low levels. Induction of all these mRNAs was observed in regenerating muscles in both the presence and absence of nerve as well as following denervation of adult fast and slow skeletal muscles. Their low level expression was maintained in adult denervated skeletal muscles but gradually suppressed in both innervated and noninnervated regenerating extensor digitorum longus muscle transplants after 2 months. Fast troponin T mRNA was synthesized in both innervated and noninnervated EDL transplants although the level of this transcript changed markedly in response to denervation of both adult fast and slow skeletal muscles. The fast troponin T mRNA containing exon 17 was also initially expressed in both regenerating muscles but its level was reduced with time in both transplants and in all adult denervated skeletal muscles. Fast and slow troponin I mRNAs were synthesised during EDL muscle regeneration in both the presence and absence of nerve but the slow troponin I expression was not maintained in noninnervated transplants. The level of fast troponin I mRNA decreased in denervated fast skeletal muscles but markedly increased in denervated Soleus. The level of slow troponin I mRNA was slightly increased in denervated fast skeletal muscles but considerably reduced in denervated Soleus.