A high density of binding sites for the ligands 3H-SCH-23390 and 3H-SKF-83566 has been found in the choroid plexus. Although these sites have similar pharmacology to D1 dopamine receptors, the high-affinity component of 3H-SCH-23390 binding in the choroid plexus has been identified as the 5-HT1c subtype of serotonin receptor. We investigated the possible role of these receptors in modulating the production of cerebrospinal fluid (CSF) in rats. (R) SCH-23390 produced up to a 50% decrease in net CSF production, compared to saline. This compound is a partial agonist at 5-HT1c serotonin receptors, and an antagonist at D1 dopamine receptors. The (S) enantiomer of SCH-23390 (SCH-23388) was ineffective. Drugs interacting with receptors for neurotransmitters in the choroid plexus may hold promise for the treatment of patients with increased intracranial pressure, including those with mass lesions, head trauma, acute or chronic hydrocephalus, or pseudotumor cerebri.