Plasmids encoding bicistronic mRNAs have been constructed and used to identify a region from the 5′ noncoding region of foot-and-mouth disease virus (FMDV) which directs efficient internal initiation of protein synthesis within cells. The loss of about 30 nucleotides (nt) from the 5′ terminus or about 50 nt from the 3′ terminus of the 435-nt region completely abolished the activity of this region. The expression of the FMDV L protease severely inhibited the expression of other genes unless they were preceded by this element. The regulation of protein synthesis mediated by FMDV is discussed.