Chromatograms with appropriate separated ganglioside fractions were overlaid with diluted patient sera, and antibody binding was detected with an alkaline phosphatase-labelled second antibody. Antiganglioside antibodies were present in the sera of 39 of 50 patients with Guillain-Barré syndrome (GBS), in 10 of 12 patients with Alzheimer's disease, and in approximately 30% of the controls. The antibodies were directed against ganglioside 3'-LM1, shown to be the major ganglioside of peripheral nerve (femoral nerve and cauda equina) in most of the positive GBS sera but also in a high proportion in the controls. No correlation was found between the severity or the course of the disease and the antibody titer. Daily parenteral administration of purified bovine brain-derived GM1 ganglioside for three months to 12 patients with Alzheimer's disease did not result in any antiganglioside GM1 antibodies. We have interpreted our findings in the following way. Human sera normally contain naturally occurring antibodies against gangliosides that in general do not cause any tissue damage. Thus, parenteral injection of gangliosides will not lead to any antibody formation.