We studied the effects of oral levetiracetam (LEV) (500 mg twice daily) in three women with stiff-person syndrome in a single-blind, placebo-controlled study. The severity of muscle rigidity and of paroxysmal symptoms was assessed by EMG and clinically by a rating scale of 0-4 and by the Patients Global Impressions Scale. LEV was well tolerated. On active treatment all patients improved as assessed by any of the objective or subjective outcome measures. No response was noticed on placebo. Our data indicate that in patients with SPS, LEV is well tolerated and has a therapeutic role in the management of both muscle stiffness and life-threatening paroxysmal respiratory spasms.