Previous research has demonstrated that free (F) and bound (B) anti-myelin basic protein (anti-MBP) can be detected in the cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS). The purpose of this report was to determine whether the immunoglobulin G (IgG) isolated from central nervous system (CNS) tissue of MS patients contains anti-MBP. IgG was detected in free and bound hydrosoluble protein extracts obtained from the brain, spinal cord and optic nerves of a patient with clinically definite and neuropathologically confirmed MS. IgG was purified from free protein extracts from brain and spinal cord by Protein G-Sepharose affinity chromatography. Anti-MBP was detected by a solid phase radioimmunoassay (RIA) in all free and bound protein extracts. Anti-MBP was isolated from purified IgG from brain and spinal cord by MBP-Sepharose affinity chromatography. Free anti-MBP in the context of whole protein extracts, within purified IgG or as purified antibody as well as tissue-bound anti-MBP in the context of whole protein extracts was completely neutralized by human MBP (h-MBP) and synthetic peptide No. 56 (residues 75-95 of h-MBP) and did not react with synthetic peptide No. 41 (residues 35-58 of h-MBP). Anti-MBP which has previously been detected in the CSF of MS patients with active disease is also present as free antibody in the extracellular space of MS-central nervous system tissue and in a smaller proportion as tissue-bound antibody.