Thyrotropin releasing hormone (TRH) in the human cerebrospinal fluid (CSF) of 102 patients with non-neurologic and neurologic diseases was measured by a specific TRH radioimmunoassay. TRH levels in CSF were 17.6 ± 3.4 pg/ml (mean ± SE) in non-neurologic diseases. TRH levels in CSF were significantly elevated in cases of spinal cord tumor and multiple sclerosis (acute phase). Elevated TRH levels in CSF were decreased in these diseases by operation or prednisolone treatment, respectively. From these data, it is suggested that TRH is present in the human CSF and that measurement of TRH levels in CSF may be a useful indicator of the activity of certain neurologic diseases.