The bacterial phosphotransferase system (PTS) is the major transport system for many carbohydrates that are phosphorylated concomitantly with the translocation step through the membrane (group translocation). It consists of two general proteins, enzyme I and histidine protein (HPr), and a series of more than 15 substrate-specific enzymes II (EII). The sequences of several of these derived from Gram-positive and Gram-negative bacteria were compared, which allowed the possible identification of the following functional domains: membrane-bound pore, substrate-binding site, linker domains, transphosphorylation domain and primary phosphorylation site. Several EIIs have been analysed in the meantime, also by topological tests, by sequential deletion of the corresponding structural genes, and by construction of intergenic hybrids between different domains of several EIIs. These data suggest evolutionary relationships between different EIIs; they also enable a general model to be constructed of EIIs as carbohydrate transport systems, phosphotransferases, chemoreceptors in chemotaxis and as part of a global regulatory network.