We assessed subclinical sympathetic hyperactivity in amyotrophic lateral sclerosis (ALS) patients, which might be followed by an autonomic spell leading to circulatory collapse, or sudden death as the disease progresses, and investigated the effect of tamsulosin hydrochloride (TSHC) on sympathetic hyperactivity. We measured the plasma norepinephrine (NE) concentrations of 41 ALS patients and 10 normal controls. TSHC, a selective alpha 1 blocker. was then administered to 10 ALS patients who had high plasma NE and to the 10 normal controls. Subsequent plasma NE change was evaluated for the possible alleviating effect of TSHC on subclinical sympathetic hyperactivity in ALS. Plasma NE was high in 20 of the ALS patients (48.8%), but had no relation to respiratory problems, which supports the previous speculation that plasma NE increases in ALS are not secondary to respiratory deficit, but reflect the primary pathomechanism of the disease. ALS patients showed a marked decrease in the NE concentration after TSHC administration, whereas there was no change in the controls. In conclusion, TSHC may be useful for suppressing central sympathetic hyperactivity, presumably the primary pathomechanism in ALS, and for preventing autonomic spells during the advanced stage of the disease.