1-(p-Chlorophenyl)piperazine (PCPP), a structural analog of p-chloroamphetamine (PCA), increased serotonin and decreased 5-hydroxyindoleacetic acid (5-HIAA) concentration in rat brain at 6 hours. At one day and one week, serotonin and 5-HIAA concentrations were normal. In contrast, PCA lowered serotonin and 5-HIAA at all three times. These different effects on 5-hydroxyindole concentrations in brain were not due to differences in brain levels of the two compounds, since these were approximately equal. PCPP lacks the ability of PCA to deplete brain 5-hydroxyindoles.