CSF/serum gradients of IgG subfractions separated by isoelectric focusing (IF) have been measured by high resolving laser densitometry. In patients with normal blood-CSF barrier permeability (N.25) and with barrier damage due to acute idiopathic polyneuropathy (N.15) and to medullary compression (N.17), the CSF/serum gradients of IgG subfractions were negatively correlated with their pI. This electrostatic selectivity appeared to be reverted in barrier damage due to acute meningoencephalitis (N.15). In a series of multiple sclerosis patients (N.31), the CSF/serum gradients of IgG subfractions lacking CSF oligoclonal bands have been used to assess the overall barrier permeability to serum IgG. All intra-BCB synthesized IgG subfractions could be measured by densitometry, whereas with other quantitative formulae, 23-26% of the results were false negatives; the total intrathecal IgG amount ranged from 0.01 to 11 mg/dl. The most frequent and prominent fractions appeared to be cathodic. Electrostatic and steric barrier selectivity must be taken into account when the amount of intrathecal IgG synthesis has to be measured.