Red blood cell and plasma cholinesterases were evaluated in control subjects and patients with the major forms of adult, sporadic motor neuron disease. For the purposes of this communication, the patients were considered as having amyotrophic lateral sclerosis (ALS) or its subtypes. Cholinesterase and acetylcholinesterase activities were evaluated and separated by dose response to their respective inhibitors. No kinetic differences were observed comparing red blood cell or plasma enzyme activities using either inhibitor. As found in previous studies, acetylcholinesterase accounted for more than 90% of acetylcholine hydrolysis in red blood cells. The plasma data were more complicated to evaluate, but at least 20% of total activity could be attributed to acetylcholinesterase. When red blood cell acetylcholinesterase activities of patients and controls were compared, no statistically significant difference was found. However, when plasma acetylcholinesterase activity was compared between the 2 groups, a statistically significant increase, almost twice the control value, was found in the ALS patients. These data may ultimately be important in the prognosis of this disease and, conceivably, could aid in understanding its pathogenesis.