The present study was undertaken to assess the impact of acute discontinuation (AD) of total parenteral nutrition (TPN) on serum glucose, insulin, and glucagon levels and on the generation of symptomatic hypoglycemia. Fifty studies were performed in 48 patients. In none of the 30 studies of 1 hour duration nor in the 20 studies of 8 hours duration was there a single episode of symptomatic hypoglycemia. One patient had a glucose below normal (60 mg/dl) during the first hour after AD. Glucose and insulin concentrations were elevated at the start of TPN discontinuation but returned to normal values within 60 minutes and remained there during the successive 7 hours of study. Although glucagon levels were slightly elevated at zero time, no significant decrease occurred. There was no evidence for counter-regulation based on the patterns of glucose and hormone levels. With some restrictions, acute discontinuation is a safe, rapid method of ending a prolonged TPN infusion.