The source of IgG in the cerebrospinal fluid (CSF) in guinea pigs with chronic relapsing experimental allergic encephalomyelitis (CR-EAE) was investigated using quotient analysis of total IgG and albumin concentrations and by computing CSF-plasma ratios of specific IgG concentrations. Increased blood-CSF barrier (B-CSFB) permeability was shown by elevated albumin quotients in both relapse and remission phases of CR-EAE and intrathecal production of IgG was indicated by raised ratios of IgG to albumin in the CSF. Intrathecal IgG synthesis was greatest in guinea pigs which had little B-CSFB damage.When enzyme-linked immunosorbent assays (ELISA) for whole cord, myelin basic protein (MBP) orMycobacterium tuberculosiswere performed with CSF and plasma adjusted to the same concentration of total IgG, the CSF/plasma ratios of ELISA results for specific antibodies were less then unity and ratios for whole cord and MBP were lower than those forM. tuberculosis.There was thus no evidence for a selective increase in the CSF of antibody specific either for the neuroantigens tested or for adjuvant components. The CSF-plasma ratios for each specific antibody were inversely correlated with the extent of total IgG intrathecal synthesis, suggesting that much of the antibody production within the CNS is the result of polyclonal B cell activation.