In this paper we report the study of tryptophan metabolism via serotonin in ventricular CSF in HIV-1 infection in order to investigate the origin of tryptophan metabolites in the human brain. The patients (n=4) were affected with noncommunicating hydrocephalus. One of these also was suffering from HIV-1 infection. The CSF was withdrawn from different sites of the cerebral cavity with a neuroendoscopic procedure which allows an accurate exploration of all the cerebral ventricles. The measurement of tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin was carried out by HPLC with fluorometric detection. In HIV-1 infection the highest concentration of tryptophan is present in the CSF of the choroid plexus; however, the levels are markedly lower than those in hydrocephalic individuals (control group). 5-Hydroxytryptophan CSF content is higher in HIV-1 infection than in hydrocephalic controls in all districts examined. Regarding serotonin, a great difference appears in the choroid plexus and in the pituitary recess between the HIV-1 infected patient and the control group. The values of 5-hydroxyindoleacetic acid are much lower in the CSF of the HIV-1 infected patient than in hydrocephalic controls. Melatonin levels appear to fluctuate largely but, in the HIV-1 infection, a great variability is present among the sites of CSF withdrawal. The third ventricle contains the highest concentration of melatonin and the choroid plexus and the pituitary recess the lowest. All the melatonin concentrations in HIV-1 infection are largely different than in hydrocephalic controls. This is the first report on the measurement of tryptophan metabolites via serotonin in ventricular CSF in HIV-1 infection.