Muscle biopsies from the lower extremities of four patients with severe tetraplegic form of diphtheritic polyneuropathy were examined by modern techniques including histochemistry, electron microscopy and morphometric procedures. Until now comparable studies have not been published. The biopsies were removed during the acute stage of the polyneuropathy. We found scattered small angulated muscle fibers beside a more generalized slight atrophy predominantly of type 2 B fibers and targetoid-phenomenons or cores in type 1 fibers. Beside this neurogenic pattern there also were, corresponding with the results of electromyography, primary myogenic alterations with different degenerative phenomenons, suspicious of toxic origin as in cardiac muscle. The intramuscular vessels showed no abnormalities except some perivascular predominantly mononuclear cellular reactions with a remarkable number of cerebriform lymphoid cells, probably T-lymphocytes. No specific pathological alterations could be detected in 11 intramuscular nerves and two motor endplates. This may reflect the more proximal demyelination of human peripheral neurons by the diphtheria toxin as found in experimental diphtheria of the rabbit in contrast to the more distal type of the guinea pig.