We sought to gain insight into the dynamics of the signalling process that initiates adaptive change in mammalian skeletal muscles in response to chronic neuromuscular stimulation. Programmable miniature stimulators were implanted into rabbits and used to impose one of the following patterns on the dorsiflexors of one ankle: 10 Hz delivered in equal on/off periods of 30 s, 30 min, or 12 h (all equivalent in terms of aggregate impulse activity to continuous 5 Hz). Two further groups received continuous stimulation at 5 Hz or 10 Hz. In every case the stimulation pattern was maintained continuously for 6 weeks. Tibialis anterior muscles stimulated intermittently with equal on/off periods of 30 s, 30 min and 12 h had contractile characteristics that were significantly slower than the contralateral, unstimulated muscles but did not differ from those of muscles stimulated continuously at 5 Hz. Muscles stimulated continuously at 10 Hz were significantly slower than either contralateral muscles or muscles stimulated with any of the other patterns. Corresponding changes were seen in myosin heavy chain isoform composition. The fatigue index, defined as the fraction of tension remaining after 5 min of a standard fatigue test, was 0.4 for muscles in the contralateral group but equal to or greater than 0.85 for muscles of all the stimulated groups. These results were interpreted with the help of a simple model of the growth and decay of a putative signalling substance based on first order kinetics. The model suggests a rate constant for the accumulation of the signalling substance that is greater than 30 h(-1), and a rate constant for its removal that is greater than 50 h(-1).