During normal development presumptive synaptic sites in the myotomes of Xenopus laevis begin to acquire a high density of ACh receptors within as little as 2 h after the arrival of the nerve fibres. Synaptic function also begins very shortly after the arrival of the nerve fibres. Initially synaptic currents are some eight times longer lasting than at maturity and are not prolonged by anticholinesterase. During the first day after nerve-muscle contact is made there is a considerable decrease in synaptic current duration, sensitivity to anticholinesterase develops, and synaptic ultrastructure becomes apparent. Schwann cells do not arrive until later. Synaptic development proceeds with a similar rapid time course in cultures of dissociated myotomes and spinal cord derived from Xenopus embryos. The cultured muscle cells also develop synaptic specializations in the absence of nerve including sites of high ACh receptor density, cholinesterase activity, and postsynaptic ultrastructure. Studies on mixed nerve and muscle cultures have further revealed that muscle impulse and contractile activity is unnecessary for the development of synaptic ultrastructure or for the localization of ACh receptors, that the localization of ACh receptors at nerve-muscle contacts is nerve-induced and involves a redistribution of surface receptors, and that the development of synaptic specializations does not occur at nerve-muscle contacts when the source of nerve is dorsal root ganglia or sympathetic ganglia rather than spinal cord.