Concentrations of homovanillic acid (HVA) were markedly elevated in the ventricular fluid of 15 children with Reye syndrome (median, 887 ng per milliliter) compared to 7 controls (median, 282 ng per milliliter), but 5-hydroxyindoleacetic acid (5-HIAA) values were comparable (medians of 198 and 189 ng per milliliter, respectively). The ratio of 5-HIAA to HVA was significantly lower in patients with Reye syndrome (0.26) than in controls (0.51). Serial samples demonstrated wide fluctuations in HVA concentration, but not in that of 5-HIAA. Monoamine metabolite concentrations were not correlated with serum ammonia, increased intracranial pressure, morbidity, or mortality. Increased HVA in Reye syndrome may reflect cerebral ischemia and release of vasoactive amines (particularly dopamine) into the brain and cerebrospinal fluid (CSF).