Two patients who underwent plasmapheresis for severe myasthenia gravis showed marked exacerbation of myasthenic weakness at the end of exchange sessions, in which citrate was used for anticoagulation. In one patient, improvement occurred after the administration of calcium but not after edrophonium. In rabbits and in rats with experimental autoimmune myasthenia gravis, decremental muscle response to 3 Hz repetitive nerve stimulation worsened significantly after injection of the citrate anticoagulant. The worsened neuromuscular transmission defect was reversed by the administration of calcium. When used for anticoagulation, citrate reduces serum ionized calcium levels and thus may aggravate myasthenic weakness and endanger patients during or immediately after plasmapheresis.