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The discovery of the oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) was a major step forward in the understanding of multiple sclerosis (MS) and other inflammatory diseases of the central nervous system. Separation of IgG molecules produced by different B cell clones was not possible until agar electrophoresis was invented in 1950. The key observation that led to the discovery of OCB can be dated back to 1959, when Karcher, van Sande and Lowenthal reported that agar electrophoresis subdivided CSF γ-globulins from a patient with subacute sclerosing panencephalitis into several individual fractions, which were distinguishable with densitometry. OCB were detected in CSF from patients with trypanosomiasis, neurosyphilis and MS by the same research group in 1960. The discovery of OCB was preceded by the detection of intrathecal IgG synthesis with Tiselilus’ moving boundary electrophoresis by Kabat in 1942. This method did not allow separation of IgG molecules produced by different B cell clones, and it is therefore a misconception that Kabat discovered the OCB. The discovery of OCB led to the still prevailing concept that MS is mediated by clonally expanded lymphocytes, and provided the basis for modern diagnostic procedures in MS. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]