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Isoelectric focusing of CSF and serum IgG followed by crossed immuno isoelectric focusing and direct immunofixation as well as quantitative assay of IgG and albumin were performed in 64 clinically definite multiple sclerosis patients. Intrathecal IgG synthesis was calculated according to the CSF IgG index and de novo CNS IgGsyn. Isoelectric focusing showed abnormal IgG fractions in CSF indicating increased intrathecal synthesis of oligoclonal IgG in 99% of patients. Only 62% and 70% of multiple sclerosis patients showed values of CSF IgG indices and de novo CNS IgGsyn higher than in controls. Increased intrathecal IgG synthesis was indicated more frequently by de novo CNS IgGsyn in patients with a normal CSF IgG index than by the CSF IgG index in patients with normal de novo CNS IgGsyn. All patients with blood CSF barrier damage had increased de novo CNS IgGsyn, but only 40% had an increased CSF IgG index. Isoelectric focusing seemed to be a more sensitive method to detect an increased intrathecal oligoclonal IgG synthesis than quantitative methods. Identification of abnormal IgG fractions can be performed easily and with more reproducible results by direct immunofixation than by crossed immuno isoelectric focusing. The formula for de novo CNS IgGsyn seemed more sensitive and less influenced by blood-CSF barrier damage than the CSF IgG index to detect increased intrathecal IgG synthesis in multiple sclerosis patients. No correlation was found between the CSF IgG pattern or amounts and age, duration, clinical course or therapy of the disease.