Immunoreactive myelin basic protein (MBP) levels were measured in cerebrospinal fluid (CSF) samples taken from 57 patients with active hydrocephalus (age range 3 weeks to 60 years). Of these patients, 28 (49%) had elevated MBP values (greater than 4.5 ng/ml). Elevated MBP levels were found in 44% of patients with congenital hydrocephalus, 75% of patients with posttraumatic hydrocephalus, 80% of patients with normal-pressure hydrocephalus, and 83% of patients with porencephaly. Also associated with abnormal MBP levels was the ventricular size as measured by computerized tomography scanning (chi 2: p less than 0.05): 36% of the patients with small ventricles (ventricle:brain ratio 0 to 0.4:1) had elevated MBP in the CSF, whereas 61% of those with moderate ventricles (0.41 to 0.6:1 ratio) and 100% of those with large ventricles (0.61 to 0.85:1 ratio) had abnormal values. Only 33% of those with maximal hydrocephalus (0.86 to 1.0:1 ratio) had elevated MBP levels, perhaps because of dilution effects. In three patients in whom CSF was obtained simultaneously by ventricular and lumbar punctures, the ventricular fluid had a consistently higher concentration of MBP, suggesting a cerebral origin. It is concluded that active hydrocephalus produces significant periventricular demyelination, probably as the result of mechanical stretching.