We have carried out a comprehensive study of the formation of muscle fibers in the human quadriceps in a large series of well dated human foetuses and children. Our results demonstrate that a first generation of muscle fibers forms between 8-10 weeks. These fibers all express slow twitch myosin heavy chain (MHC) in addition to embryonic and foetal MHCs, vimentin and desmin. Between 10-11 weeks, a subpopulation of these fibers express slow tonic MHC, being the first primordia of muscle spindles. Extrafusal fibers of a second generation form progressively and asynchronously around the primary fibers between 10-18 weeks, giving the muscle a very heterogeneous aspect due to different degrees of organization of their proteins. By 20 weeks, these second generation fibers become homogeneous and thereafter undergo a process of maturation and differentiation when they eliminate vimentin, embryonic and foetal MHCs to express either slow twitch or fast MHC. The differentiation of these second generation fibers into slow and fast depends upon different factors, such as motor innervation or level of thyroid hormone. Around the intrafusal first generation fibers, additional subsequent generations of fibers are also progressively formed. Some differ from the extrafusal second generation fibers by expressing slow tonic MHC, others by continuous expression of foetal MHC. The differentiation of intrafusal fibers is probably under the influence of both sensory and motor innervation.