We investigated the effects of muscle loss and limitation of daily activities on sympathetic outflow to muscles by measuring muscle sympathetic nerve activity (MSNA) in 12 patients with amyotrophic lateral sclerosis (ALS) as compared with other 15 neuromuscular patients (controls). The burst incidence of MSNA at rest was significantly higher in patients with ALS, even in elderly patients, compared with controls (p < 0.01). There were no differences in the level of disability, heart rate or blood pressure at rest between two groups. Blood pressure and MSNA were less changed by head-up tilting in patients with ALS compared with controls. MSNA of ALS was not correlated with the disability score, PaO2, PaCO2, forced vital capacity, the disease duration or prognosis. MSNA at rest was increased in ALS patients, regardless of the severity of muscle loss or disability. It might be suggested that autonomic motor neurons seem to become affected by the same pathologic process that kills motor neurons.