We studied the variation in immunoglobulin G (IgG) and albumin concentrations in serial sampling of the first 25 ml of CSF during lumbar puncture (LP). A linear decremental gradient averaged 15% for both IgG and albumin. Both direction and magnitude of the gradient were unaffected by the position of the patient. In 12 patients with MS, the CSF IgG: albumin quotient was 5.5% greater when computed from the last aliquot, but this difference was not significant. These protein gradients affect the absolute concentrations but arae not likely to affect the interpretation of immunoglobulin indices or electrophoresis patterns.