As an aid in the development of vector systems for use in gene therapy paradigms of central nervous system disorders such as Parkinson's disease, we have developed L-Dopa or dopamine-producing gene cassettes. Specifically, a human tyrosine hydroxylase cDNA (HTH-2) was rendered constitutively active by truncation of the N-terminal regulatory domain (tHTH). In addition, a bicistronic construct capable of directing the production of dopamine was created by inserting an internal ribosome entry site downstream of tHTH followed by the coding sequences of aromatic amino acid decarboxylase. All three constructs generated immunoreactive peptides of the predicted size, were enzymatically active, and produced L-Dopa (HTH-2, tHTH) or dopamine (bicistronic construct) following transient transfection of COS-7 cells. These constructs, in conjunction with viral or nonviral expression systems, may be efficacious in gene therapy approaches to Parkinson's disease.