Application of membrane-permeable analogues of adenosine 3',5'-(cyclic)monophosphate (cAMP) or forskolin to embryonic muscle cells of 1-day-old Xenopus cultures altered the response of the myocyte to iontophoretically applied acetylcholine (ACh). The initial amplitude and the decay time of the ACh-induced currents were elevated, and the rate of ACh-induced channel desensitization was increased. Single-channel recordings showed that cAMP analogues increased the mean open time of the low-conductance ACh channels, without affecting the single-channel conductance. Interestingly, this effect on ACh channels disappeared in myocytes of 3-day-old cultures, suggesting developmental changes in the susceptibility of the ACh channel to modulation. A possible involvement of cAMP in modulating the synaptic activity of early developing synapses was further indicated by prolonged decay times of spontaneous synaptic currents following treatment with dibutyryl-cAMP (Bt2cAMP). Factors released from the nerve terminals, if they activate the muscle adenylate cyclase system, could thus enhance the synaptic response during synaptogenesis.