Summary 1. The newborn, germfree piglet soon develops a state of severe hypogly-cemia with a corresponding decline in general metabolism unless glucose is present in the available diet. Our finding of a virtual absence of intestinal lactase activity (β-galacto-sidase) in the small intestine of axenic piglets suggests a failure of hydrolysis of lactose in the sterile, homogenized cow's milk feedings. 2. Our preliminary studies with germ-free piglets reveal similar hepatic glucose-6-phosphatase activities between the normo-glycemic (SPF) and hypoglycemic (GF) pigs. The activity of hepatic phosphoryl-ase was also essentially the same for the normoglycemic (SPF) and hypoglycemic (GF) piglets and was in the range of activity usually found in normal rat liver. 3. Since blood glucose concentration depends upon the balance between entry, alimentary or hepatic, and removal, utilization and storage, a comprehensive study of the hypoglycemic syndrome in the piglet involves several parameters. Rate of glucose utilization and failure of hepatic glucose formation await further study.