Acetylcholinesterase (AChE) molecular forms in denervated rat muscles, as revealed by velocity sedimentation in sucrose gradients, were examined from three aspects: possible differences between fast and slow muscles, response of junctional vs extrajunctional AChE, and early vs late effects of denervation. In the junctional region, the response of the asymmetric AChE forms to denervation is similar in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle: (a) specific activity of the A12 form decreases rapidly but some persists throughout and even increases after a few weeks; (b) an early and transient increase of the A4 AChE form lasting for a few weeks may be due to a block in the synthetic process of the A12 form. In the extrajunctional regions, major differences with regard to AChE regulation exist already between the normal EDL and SOL muscle. The extrajunctional asymmetric AChE forms are absent in the EDL because they became completely repressed during the first month after birth, but they persist in the SOL. Differences remain also after denervation and are, therefore, not directly due to different neural stimulation patterns in both muscles: (a) an early but transient increase of the G4 AChE occurs in the denervated EDL but not in the SOL; (b) no significant extrajunctional activity of the asymmetric AChE forms reappears in the EDL up till 7 wk after denervation. In the SOL, activity of the asymmetric AChE forms is decreased early after denervation but increases thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)