Using a radioimmunological method performed in the presence and absence of the acetylcholine agonist decamethonium (DC), it was demonstrated that 98% of myasthenia gravis (MG) patients' sera (positive for anti-acetylcholine receptor (anti-AChR) antibody titres in the conventional assay) contain antibodies that block the binding of alpha bungarotoxin (alpha Bgt) to human AChR. The positive effect of myasthenic immunoglobulins against the alpha Bgt toxicity was revealed by a test devised to investigate the biological significance of these blocking antibodies in vivo in Balb/c mice. IgG from sera containing blocking antibodies, detected either directly or in the presence of DC, protected the mice treated (24 of 25); nevertheless no overt clinical signs of a myasthenic syndrome were observed. Control IgG, from normal human sera or from a systemic lupus erythematosus patient, provided no protection (22 dead out of 26). IgG from MG sera devoid of anti-AChR antibodies (eight out of eight) and IgG from serum containing anti-AChR antibodies but devoid of blocking antibodies offered no defence against alpha Bgt toxicity (13 dead out of 15). The pathological role of blocking antibodies, cell mediated immunity or other mechanisms is discussed.