In the Rett syndrome (RS), a progressive encephalopathy affecting girls, deficient neurotransmitter synthesis has been suggested as a pathogenetic mechanism. Nine girls with RS were treated with 0.3 g of tyrosine and 0.1 g of tryptophan per kg body weight for 2 to 17 weeks. This resulted in a median rise in the spinal fluid concentration of the dopamine metabolite homovanillic acid by 31%, and of the serotonin metabolite 5-hydroxyindoleacetic acid by 40%. This finding supports the hypothesis of a compromised neurotransmitter synthesis and indicates that it can be stimulated by supply of amino acid precursors. A double-blind cross-over trial including 11 girls did not show clinical improvement during a treatment period of 8 to 10 weeks.