Intrathecal immunoglobulin synthesis and activation of the complement cascade occurs in patients with multiple sclerosis (MS). The present study aimed at further studying the relation between intrathecal immunoglobulin synthesis and complement activation. We compared total intrathecal synthesis of lgA, IgG, and IgM, the number of cells secreting anti-myelin basic protein (MBP) and anti-proteolipid protein (PLP) antibodies of the IgG isotype and intrathecal activation of the complement cascade in patients with possible onset symptoms of MS (n=18) or clinically definite MS (n=30). Early activation of the complement cascade correlated with intrathecal synthesis of IgM. Intrathecal IgG, lgA and IgM synthesis also correlated weakly with the presence of cells secreting anti-MBP or anti-PLP autoantibodies. Full activation of the complement cascade did not correlate with any measures of intrathecal antibody synthesis. These findings suggest a complex relation between different immunoglobulin isotypes and complement activation which may have similarly complex roles in the pathogenesis of MS.