We investigated the role of the neural tube in muscle cell differentiation in developing somitic myotome of chick embryo, particularly through fast myosin heavy chain (MHC) isoform expression. An embryonic fast MHC labeled with EB165 mAb was expressed in somitic cells from stage 15 of Hamburger and Hamilton (H.H.) (24 somites). Moreover, a distinct early embryonic fast MHC was expressed only from stage 15 of H.H. to stage 36 (E10). Like neonatal MHC, this isoform was labeled with 2E9 mAb but differed in its immunopeptide mapping. Expression of EB165-labeled embryonic fast MHC occurred in somitic myotomes deprived of neural tube influence by in ovo ablation as well as in somite explants cultured alone in vitro. Conversely, ablation of the neural tube prevented somitic expression of MHC labeled with 2E9 mAb. The neural tube induced in vitro expression of this MHC in explants of somites which failed to express it when cultured alone. These results indicate that signals emanating from the neural tube are required for the expression of early embryonic fast MHC isoform in developing somitic myotome.