We studied the effect of botulinum toxin A (BTA) on painful muscular spasms and rigidity in two bedridden patients with clinical, electrophysiologic, and immunologic evidence of stiff-person syndrome. We injected BTA of saline solution into several limb muscles with both the rater and patient blinded to the order of the injections. A physician, unaware of the treatment order, used an objective rating scale for rigidity and spasm frequency scale and independently assessed the treatment results. BTA administration significantly reduced rigidity and stopped the spasms in all limbs. Following BTA injection on one side, the spasm frequency decreased bilaterally possibly because of the spread of hematogenous toxin.