The assessment of intrathecally synthesised immunoglobulin is an important part of routine cerebrospinal fl uid (CSF) analysis. Immunoglobulins can be detected in normal CSF and are derived from plasma. The appearance of immunoglobulins in normal CSF is readily explained by size-dependent diffusion across blood-CSF barriers, and their concentrations increase with the general increase in CSF protein concentrations observed in a wide range of neurological diseases. Therefore, methods that take the normal diffusion of immunoglobulins into account are needed for quantitative assessment of intrathecal immunoglobulin synthesis. Intrathecally synthesised immunoglobulins are usually of restricted clonality, and electrophoresis-based methods can be used for detecting this in the form of oligoclonal bands. These methods depend on comparing paired CSF and blood samples. Qualitative analyses for the assessment of intrathecally synthesised oligoclonal bands are more technically demanding, but are more sensitive for the detection of intrathecal immunoglobulin synthesis, and are less susceptible to artefacts induced by blood-CSF barrier disturbances than quantitative methods. The same general principles apply both for the detection of total intrathecal immunoglobulin synthesis and for the detection of specifi c antibody responses in infectious or autoimmune conditions.