Gene therapy vectors that can be targeted to motoneuronal cells are required in the field of neurodegenerative diseases. We propose the use of the atoxic fragment C of tetanus toxin (TTC) as biological activity carrier to the motoneurons. Naked DNA encoding beta-galactosidase-TTC hybrid protein was used to transfect muscle cells in vivo, resulting in a selective gene transfer of the enzymatic activity to the CNS. In the muscle, level expression of beta-galactosidase was readily detectable 24 h after injection, reaching a maximum after 4 days and gradually decreasing thereafter. Labelling in the hypoglossal motoneurons and motor cortex was observed from 4 days after injection. In this paper, we show that TTC works as an enzymatic activity carrier to the CNS when muscle cells are transfected in vivo. We have also shown that the presence of TTC does not have any influence on the expression of the transfected gene. Both these results warrant further studies of TTC as a means of treating motoneuron diseases in the field of gene therapy.