The biogenic amines, dopamine, serotonin, and noradrenaline, and their respective metabolites, homovanillic acid, 5-hydroxyindoleacetic acid, and hydroxymethoxyphenylglycol, were measured in selected brain regions obtained at postmortem examination from 4 patients, ages 12-30 years, with typical features of Rett syndrome. A 50% or greater reduction in each compound, except hydroxymethoxyphenylglycol, was observed in the substantia nigra from the 2 older patients, while the youngest patient had normal or nearly normal levels. These results correspond with the most consistent neuropathologic finding in Rett syndrome, reduced melanin content in neurons of the substantia nigra.