Previous studies in our laboratory have shown that tetrahydrobiopterin (BH4) activates a sine hydroxylase phosphatase in vitro. The present results,are consistent with these earlier findings and suggest that BH4 has a similar effect in intact rat striatal synaptosomes. An increase in intrasynaptosomal BH4, caused by the intake of exogenous pterin, produced an increase in the dephosphorylation of tyrosine hydroxylase in intact synaptosomes. The effect was rapid and concentration dependent. Moreover, the response appeared to be specific for BH4. A similar and reversible effect was observed with the BH4 precursor sepiapterin, whereas biopterin was virtually inactive. Future studies will continue to address this novel regulatory function with a view to characterizing further the mode of action of BH4 and its biological significance in vivo. Other studies have used rat striatal slices to examine the role of tyrosine hydroxylase in the brain during hyperphenylalanemic states. Specifically, the relative contribution to the protein-bound tyrosine of endogenously formed 3H-tyrosine from exogenous 3H-phenylalanine was compared to that from exogenous l4C-tyrosine. Newly formed 3H-tyrosine incorporation into protein was demonstrated. This 3H-tyrosine incorporation was dependent on the concentration of exogenous 3H-phenylalanine.