Rats treated with haloperidol or bearing subcutaneous implants of prolactin-secreting tumors had elevated CSF prolactin levels compared to those observed in control rats. These levels were commensurate with the increased serum level of prolactin, although there appeared to be an upper limit to the CSF prolactin concentration. Patients with prolactin-secreting pituitary adenomas had elevated CSF hormone levels as compared to patients with non-endocrine neurologic disease. This obtained, regardless of whether the tumor was intra- or extrasellar in its growth. The implications for the route of entry of prolactin into CSF under both normal and abnormal conditions, and the potential role for CSF prolactin as part of a feedback regulatory system on pituitary prolactin release are discussed.